Heidi Mansour

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Courses

Scholarly Contributions

Books

• Hickey, A. J., & Mansour, H. M. (2019). Inhalation Aerosols: Physical and Biological Basis for Therapy. Hickey, A.J. and Mansour, H.M. (Editors). 3rd Edition-Revised & Expanded. Informa Healthcare/Taylor & Francis/CRC Press.. London, United Kingdom.: Informa Healthcare/Taylor & Francis/CRC Press.
• Kumar, A., Mansour, H. M., Friedman, A., & Blough, E. (2013). Nanomedicine in Drug Delivery. London, United Kingdom.: Informa Healthcare/Taylor & Francis/CRC Press.

Chapters

• Mansour, H. M., Black, S. M., Fineman, J. R., Yuan, J. X., Hayes, D., & Acosta, M. F. (2019). Chapter 19: Therapeutics in Pulmonary Hypertension. In Inhalation Aerosols: Physical and Biological Basis for Therapy. Hickey, A.J. and Mansour, H.M. (Editors). 3rd Edition-Revised & Expanded. Informa Healthcare/Taylor & Francis/CRC Press.(pp 313-322). London, United Kingdom.: Informa Healthcare/Taylor & Francis/CRC Press.
• Mansour, H. M., Hayes, D., & Muralidharan, P. (2019). Chapter 18: Pulmonary Fibrosis. In Inhalation Aerosols: Physical and Biological Basis for Therapy. Hickey, A.J. and Mansour, H.M. (Editors). 3rd Edition-Revised & Expanded. Informa Healthcare/Taylor & Francis/CRC Press.(pp 303-312). London, United Kingdom.: Informa Healthcare/Taylor & Francis/CRC Press.
• Mansour, H. M., Ledford, J. G., Black, S. M., & Droopad, D. (2019). Chapter 20: Overview of Lung Surfactant and Respiratory Distress Syndrome. In Inhalation Aerosols: Physical and Biological Basis for Therapy. Hickey, A.J. and Mansour, H.M. (Editors). 3rd Edition-Revised & Expanded. Informa Healthcare/Taylor & Francis/CRC Press.(pp 323-326). London, United Kingdom.: Informa Healthcare/Taylor & Francis/CRC Press.
• Mansour, H. M., Smyth, H. D., Kim, Y. J., Williams III, R. O., & Warnkin, Z. (2019). Chapter 22: Fundamentals in Nasal Drug Delivery. In Inhalation Aerosols: Physical and Biological Basis for Therapy. Hickey, A.J. and Mansour, H.M. (Editors). 3rd Edition-Revised & Expanded. Informa Healthcare/Taylor & Francis/CRC Press.(pp 343-360). London, United Kingdom.: Informa Healthcare/Taylor & Francis/CRC Press.
• Mansour, H. M., Myrdal, P. B., Younis, U., Muralidharan, P., Hillery, A. M., & Hayes Jr, D. (2016). Book Chapter 11: Pulmonary Drug Delivery.. In Drug Delivery: Fundamentals & Applications.(pp 249-277). London, United Kingdom.: CRC Press/Taylor & Francis, Inc.
• Mansour, H. M., Park, C., & Bawa, R. (2016). Book Chapter 9: Design and Development of Approved Nanopharmaceutical Products.. In Handbook of Clinical Nanomedicine: From Bench to Bedside. Bawa, R., Audette, G.F., and Rubinstein, I. (Editors)(pp 233-272). Boca Raton, FL.: CRC Press/Taylor & Francis, Inc.
• Mansour, H. M., Muralidharan, P., & Hayes, Jr., D. (2015). Book Chapter 8b: Inhaled Nanoparticulate Systems: Composition, Manufacture, and Aerosol Delivery.. In The ISAM Textbook of Aerosol Medicine.(pp 353-394). Rochelle, NY.: International Society of Aerosols in Medicine (ISAM)/Mary Ann Libert Publishing, Inc.
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  Mansour, H.M., Muralidharan, P., and Hayes, D. Jr. Book Chapter 8b: Inhaled Nanoparticulate Systems: Composition, Manufacture, and Aerosol Delivery. The ISAM Textbook of Aerosol Medicine. Dhand, R. (Editor-in-Chief), International Society of Aerosols in Medicine (ISAM)/Mary Ann Libert Publishing, Inc. Rochelle, NY. (2015): 353-394.
• Mansour, H. M., Xu, Z., Meenach, S. A., Park, C., Rhee, Y., & Deluca, P. P. (2015). Book Chapter 5: Novel Drug Delivery Systems.. In Drug Delivery.(pp pp.71-107). Burlington, MA.: Jones & Bartlett,.
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  Mansour, H.M., Xu, Z., Meenach, S.A., Park, C.W., Rhee, Y.S., and DeLuca, P.P. Book Chapter 5: Novel Drug Delivery Systems. Drug Delivery. 550 pages. Mitra, A.K. (Editor), Jones & Bartlett, Burlington, MA. (2015): pp.71-107. ISBN-13: 9781284025682

Journals/Publications

• Acosta, M. F., Abrahamson, M. D., Encinas-Basurto, D., Fineman, J. R., Black, S. M., & Mansour, H. M. (2020). Inhalable Nanoparticles/Microparticles of an AMPK and Nrf2 Activator for Targeted Pulmonary Drug Delivery as Dry Powder Inhalers. The AAPS journal, 23(1), 2.
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  Metformin is an activator of the AMPK and Nrf2 pathways which are important in the pathology of several complex pulmonary diseases with unmet medical needs. Organic solution advanced spray drying in the absence of water in closed-mode was used to design and develop respirable dry powders. Following comprehensive characterization, the influence of physicochemical properties was correlated with performance as aerosols using inertial impaction and three different human dry powder inhaler (DPI) devices varying in device properties. In vitro cell assays were conducted to test safety in 2D human pulmonary cell lines and in 3D small airway epithelia comprising primary cells at the air-liquid interface (ALI). In addition, in vitro transepithelial electrical resistance (TEER) was carried out. Metformin remained crystalline following advanced spray drying under these conditions. All SD powders consisted of nanoparticles/microparticles in the solid state. In vitro aerosol dispersion performance showed high aerosolization for all SD metformin powders with all DPI devices tested. High emitted dose for all powders with all three DPI devices was measured. Differences in other aerosol performance parameters and the interplay between the properties of different formulations produced at specific pump rates and the three different DPI devices were correlated with spray drying pump rate and device properties. Safety over a wide metformin dose range was also demonstrated in vitro. Aerosol delivery of metformin nanoparticles/microparticles has the potential to be a new "first-in-class" therapeutic for the treatment of a number of pulmonary diseases including pulmonary vascular diseases such as pulmonary hypertension.
• Alabsi, W., Al-Obeidi, F. A., Polt, R., & Mansour, H. M. (2020). Organic Solution Advanced Spray-Dried Microparticulate/Nanoparticulate Dry Powders of Lactomorphin for Respiratory Delivery: Physicochemical Characterization, In Vitro Aerosol Dispersion, and Cellular Studies. Pharmaceutics, 13(1).
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  The purpose of this study was to formulate Lactomorphin (MMP2200) in its pure state as spray-dried(SD) powders, and with the excipient Trehalose as co-spray-dried(co-SD) powders; for intranasal and deep lung administration with Dry Powder Inhalers (DPI). Lactomorphin is a glycopeptide which was developed for the control of moderate to severe pain. Particles were rationally designed and produced by advanced spray drying particle engineering in a closed mode from a dilute organic solution. Comprehensive physicochemical characterization using different analytical techniques was carried out to analyze the particle size, particle morphology, particle surface morphology, solid-state transitions, crystallinity/non-crystallinity, and residual water content. The particle chemical composition was confirmed using attenuated total reflectance-Fourier-transform infrared (ATR-FTIR), and Confocal Raman Microscopy (CRM) confirmed the particles' chemical homogeneity. The solubility and Partition coefficient (LogP) of Lactomorphin were determined by the analytical and computational methodology and revealed the hydrophilicity of Lactomorphin. A thermal degradation study was performed by exposing samples of solid-state Lactomorphin to a high temperature (62 °C) combined with zero relative humidity (RH) and to a high temperature (62 °C) combined with a high RH (75%) to evaluate the stability of Lactomorphin under these two different conditions. The solid-state processed particles exhibited excellent aerosol dispersion performance with an FDA-approved human DPI device to reach lower airways. The cell viability resazurin assay showed that Lactomorphin is safe up to 1000 μg/mL on nasal epithelium cells, lung cells, endothelial, and astrocyte brain cells.
• Gomez, A. I., Acosta, M. F., Muralidharan, P., Yuan, J. X., Black, S. M., Hayes, D., & Mansour, H. M. (2020). Advanced spray dried proliposomes of amphotericin B lung surfactant-mimic phospholipid microparticles/nanoparticles as dry powder inhalers for targeted pulmonary drug delivery. Pulmonary pharmacology & therapeutics, 64, 101975.
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  The purpose of this study was to design, develop and characterize inhalable proliposomal microparticles/nanoparticles of Amphotericin B (AmB) with synthetic phospholipids, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) which are lung surfactant-mimic phospholipids. Organic solutions of AmB and phospholipids, were co-spray dried using an advanced closed-mode system and a high performance cyclone. Scanning electron microscopy (SEM) was employed to visualize the surface structure, morphology, and particles size. The residual water content of the proliposomes was quantified by Karl Fisher coulometric titration (KFT). Degree of crystallinity/non-crystallinity was measured by X-ray powder diffraction (XRPD). Phase behavior was measured by differential scanning calorimetry. The chemical composition by molecular fingerprinting was established using attenuated total reflectance (ATR)-Fourier-transform infrared (FTIR) spectroscopy. The amount of AmB loaded into the proliposomes was quantified using UV-VIS spectroscopy. The in vitro aerosol dispersion performance was conducted using the Next Generation Impactor (NGI) and the human dry powder inhaler (DPI) (Handihaler®) that is FDA-approved. Different human lung cell lines were employed to demonstrate in vitro safety as a function of dose and formulation. Smooth, spherical microparticles/nanoparticles were formed at medium and high spray drying pump rates and had low residual water content. A characteristic peak in the XRPD diffraction pattern as well as an endotherm in DSC confirmed the presence of the lipid bilayer structure characteristic in the DPPC/DPPG proliposomal systems. Superior in vitro aerosol performance was achieved with engineered microparticles/nanoparticles demonstrating suitability for targeted pulmonary drug delivery as inhalable dry powders. The in vitro cellular studies demonstrated that the formulated proliposomes are safe. These AmB proliposomes can be a better option for targeted treatment of severe pulmonary fungal infections.
• Mashaqi, S., Mansour, H. M., Alameddin, H., Combs, D., Patel, S., Estep, L., & Parthasarathy, S. (2020). Matrix metalloproteinase-9 as a messenger in the crosstalk between obstructive sleep apnea and comorbid systemic hypertension, cardiac remodeling, and ischemic stroke: a literature review. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.
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  Obstructive sleep apnea is a common sleep disorder. There is a strong link between sleep related breathing disorders and cardiovascular and cerebrovascular diseases. Matrix metalloproteinase-9 (MMP-9) is a biological marker for extracellular matrix degradation which plays a significant role systemic hypertension, myocardial infarction and post-MI heart failure, and ischemic stroke. This manuscript reviews MMP-9 as an inflammatory mediator and a potential messenger between OSA and OSA-induced comorbidities.
• Mitchell, J. P., Berlinski, A., Canisius, S., Cipolla, D., Dolovich, M. B., Gonda, I., Hochhaus, G., Kadrichu, N., Lyapustina, S., Mansour, H. M., Darquenne, C., Clark, A. R., Newhouse, M., Ehrmann, S., Humphries, R., & Boushey, H. (2020). Urgent Appeal from International Society for Aerosols in Medicine (ISAM) During COVID-19: Clinical Decision Makers and Governmental Agencies Should Consider the Inhaled Route of Administration: A Statement from the ISAM Regulatory and Standardization Issues Networking Group. Journal of aerosol medicine and pulmonary drug delivery, 33(4), 235-238.
• Muralidharan, P., Jones, B., Allaway, G., Biswal, S. S., & Mansour, H. M. (2020). Design and development of innovative microparticulate/nanoparticulate inhalable dry powders of a novel synthetic trifluorinated chalcone derivative and Nrf2 agonist. Scientific reports, 10(1), 19771.
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  Chalcone derivatives are shown to possess excellent anti-inflammatory and anti-oxidant properties which are of great interest in treating respiratory diseases such as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF). This study successfully designed and developed dry powder inhaler (DPI) formulations of TMC (2-trifluoromethyl-2'-methoxychalone), a new synthetic trifluorinated chalcone and Nrf2 agonist, for targeted pulmonary inhalation aerosol drug delivery. An advanced co-spray drying particle engineering technique was used to design and produce microparticulate/nanoparticulate formulations of TMC with a suitable excipient (mannitol) as inhalable particles with tailored particle properties for inhalation. Raw TMC and co-spray dried TMC formulations were comprehensively characterized for the first time using scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) spectroscopy, thermal analysis, X-ray powder diffraction (XRPD), and molecular fingerprinting as dry powders by ATR-FTIR spectroscopy and Raman spectroscopy. Further, biocompatibility and suitability of formulations were tested with in vitro cellular transepithelial electrical resistance (TEER) in air-interface culture (AIC) using a human pulmonary airway cell line. The ability of these TMC formulations to perform as aerosolized dry powders was systematically evaluated by design of experiments (DOEs) using three different FDA-approved human inhaler devices followed by interaction parameter analyses. Multiple spray drying pump rates (25%, 75%, and 100%) successfully produced co-spray dried TMC:mannitol powders. Raw TMC exhibited a first-order phase transition temperature at 58.15 ± 0.38 °C. Furthermore, the results demonstrate that these innovative TMC dry powder particles are suitable for targeted delivery to the airways by inhalation.
• Muralidharan, P., Mallory, E. K., Malapit, M., Phan, H., Ledford, J. G., Hayes, D., & Mansour, H. M. (2020). Advanced design and development of nanoparticle/microparticle dual-drug combination lactose carrier-free dry powder inhalation aerosols. RSC advances, 10(68), 41846-41856.
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  : lactose is the only FDA-approved carrier for dry powder inhaler (DPI) formulations in the US. Lactose carrier-based DPI products are contraindicated in patients with a known lactose allergy. Hence, inhaler formulations without lactose will benefit lactose allergic asthmatics. : to rationally design and develop lactose carrier-free dry powder inhaler formulations of fluticasone propionate and salmeterol xinafoate that will benefit people with known lactose allergy. The study also aims at improving the aerosol deposition of the dry powder formulation through advanced particle engineering design technologies to create inhalable powders consisting of nanoparticles/microparticles. : advanced DPI nanoparticle/microparticle formulations were designed, developed and optimized using organic solution advanced closed-mode spray drying. The co-spray dried (co-SD) powders were comprehensively characterized in solid-state and comparative analysis of the aerodynamic performance of these molecularly mixed formulations was conducted with the marketed formulation of Advair® Diskus® interactive physical mixture. : comprehensive solid-state physicochemical characterization of the powders showed that the engineered co-SD particles were small and spherical within the size range of 450 nm to 7.25 μm. Improved fine particle fraction and lower mass median aerodynamic diameter were achieved by these DPI nanoparticles/microparticles. : this study has successfully produced a lactose-free dry powder formulation containing fluticasone propionate and salmeterol xinafoate with mannitol as excipient engineered as inhalable DPI nanoparticles/microparticles by advanced spray drying. Further, co-spray drying with mannitol and using Handihaler® device can generate higher fine particle mass of fluticasone/salmeterol. Mannitol, a mucolytic agent and aerosol performance enhancer, is a suitable excipient that can enhance aerosol dispersion of DPIs.
• Hayes, D., Nance, A. E., & Mansour, H. M. (2018). Sigh Syndrome in Pediatric Asthma. Lung.
• Li, S. S., Tumin, D., Krone, K. A., Boyer, D., Kirkby, S. E., Mansour, H. M., & Hayes, D. (2018). Risks associated with lung transplantation in cystic fibrosis patients. Expert review of respiratory medicine, 12(11), 893-904.
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  Survival after lung transplantation lags behind outcomes of other solid organ transplants, and complications from lung transplant are the second most common cause of death in cystic fibrosis. Evolving surgical techniques, therapeutics, and perioperative management have improved short-term survival after lung transplantation, yet have not translated into significant improvement in long-term mortality. Areas covered: We review risk factors for poor long-term outcomes among patients with cystic fibrosis undergoing lung transplantation to highlight areas for improvement. This includes reasons for organ dysfunction, complications of immunosuppression, further exacerbation of extrapulmonary complications of cystic fibrosis, and quality of life. A literature search was performed using PubMed-indexed journals. Expert commentary: There are multiple medical and socioeconomic barriers that threaten long-term survival following lung transplant for patients with cystic fibrosis. An understanding of the causes of each could elucidate treatment options. There is a lack of prospective, multicenter, randomized control trials due to cost, complexity, and feasibility. Ongoing prospective studies should be reserved for the most promising interventions identified in retrospective studies in order to improve long-term outcomes.
• Mansour, H. M. (2018). Inhaled medical aerosols by nebulizer delivery in pulmonary hypertension. Pulmonary circulation, 8(4), 1-2.
• Acosta, M. F., Muralidharan, P., Meenach, S. A., Hayes, D., M-Black, S., & Mansour, H. M. (2016). In Vitro Pulmonary Cell Culture in Pharmaceutical Inhalation Aerosol Delivery: 2-D, 3-D, and In Situ Bioimpactor Models. Current pharmaceutical design, 22(17), 2522-31.
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  The use of non-invasive inhaled aerosols for pulmonary drug delivery continues to grow. This is due to the many unique advantages this delivery route offers for the treatment of both local and systemic diseases. The physicochemical properties of the formulated drugs as well as the physiology of the lungs play a key role in both the deposition and absorption of the particles. The airway and the alveolar epithelium are targets for the treatment of respiratory diseases. However, particles have to overcome biological barriers before they reach their target and produce an effect.
• Hayes, D., Auletta, J. J., Whitson, B. A., Black, S. M., Kirkby, S., Tobias, J. D., & Mansour, H. M. (2016). Human leukocyte antigen mismatching and survival after lung transplantation in adult and pediatric patients with cystic fibrosis. The Journal of thoracic and cardiovascular surgery, 151(2), 549-57.e1.
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  The influence of human leukocyte antigen (HLA) mismatching on survival in adult and pediatric patients with cystic fibrosis (CF) after lung transplantation (LTx) is unknown.
• Hayes, D., Black, S. M., Tobias, J. D., Kirkby, S., Mansour, H. M., & Whitson, B. A. (2016). Influence of Pulmonary Hypertension on Patients With Idiopathic Pulmonary Fibrosis Awaiting Lung Transplantation. The Annals of thoracic surgery, 101(1), 246-52.
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  The influence of varying levels of pulmonary hypertension (PH) on survival in idiopathic pulmonary fibrosis is not well defined.
• Hayes, D., Black, S. M., Tobias, J. D., Kopp, B. T., Kirkby, S. E., Mansour, H. M., & Whitson, B. A. (2016). Influence of human leukocyte antigen mismatching on bronchiolitis obliterans syndrome in lung transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 35(2), 186-94.
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  Varying results have been reported in the investigation of human leukocyte antigen (HLA) mismatching and bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx).
• Hayes, D., Black, S. M., Tobias, J. D., Mansour, H. M., & Whitson, B. A. (2016). Prevalence of Pulmonary Hypertension and its Influence on Survival in Patients With Advanced Chronic Obstructive Pulmonary Disease Prior to Lung Transplantation. COPD, 13(1), 50-6.
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  Prevalence of pulmonary hypertension (PH) and its influence on survival in chronic obstructive pulmonary disease (COPD) are not well studied in the lung allocation score (LAS) era.
• Hayes, D., Kopp, B. T., Kirkby, S. E., Reynolds, S. D., Mansour, H. M., Tobias, J. D., & Tumin, D. (2016). Impact of Donor Arterial Partial Pressure of Oxygen on Outcomes After Lung Transplantation in Adult Cystic Fibrosis Recipients. Lung, 194(4), 547-53.
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  Donor PaO2 levels are used for assessing organs for lung transplantation (LTx), but survival implications of PaO2 levels in adult cystic fibrosis (CF) patients receiving LTx are unclear.
• Hayes, D., McConnell, P. I., Yates, A. R., Tobias, J. D., Galantowicz, M., Mansour, H. M., & Tumin, D. (2016). Induction immunosuppression for combined heart-lung transplantation. Clinical transplantation, 30(10), 1332-1339.
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  Research on induction immunosuppression in patients undergoing combined heart-lung transplantation (HLTx) is limited.
• Hayes, D., Tumin, D., Yates, A. R., Mansour, H. M., Nicol, K. K., Tobias, J. D., & Palmer, A. F. (2016). Transfusion with packed red blood cells while awaiting lung transplantation is associated with reduced survival after lung transplantation. Clinical transplantation, 30(12), 1545-1551.
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  The effect of pretransplant transfusion of red blood cells on survival after lung transplantation (LTx) has not been studied.
• Hayes, D., Younger, B. R., Mansour, H. M., & Strawbridge, H. (2016). Precordial Catch Syndrome in Elite Swimmers With Asthma. Pediatric emergency care, 32(2), 104-6.
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  Precordial catch syndrome is a benign cause of chest pain in children and adolescents that remains underrecognized. Because of distinctive symptoms, precordial catch syndrome is not necessarily a diagnosis of exclusion. However, a detailed history eliciting diagnostic features is important, along with a physical examination excluding other pathologic disorders. We present the cases of 2 elite swimmers with asthma who had acute episodes of precordial catch syndrome, one associated with an acute asthma exacerbation and one not, while swimming during competitive swim meets that required rescue efforts for both and eventual evaluation in the emergency department.
• Meenach, S. A., Tsoras, A. N., McGarry, R. C., Mansour, H. M., Hilt, J. Z., & Anderson, K. W. (2016). Development of three-dimensional lung multicellular spheroids in air- and liquid-interface culture for the evaluation of anticancer therapeutics. International journal of oncology, 48(4), 1701-9.
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  Three-dimensional (3D) lung multicellular spheroids (MCS) in liquid-covered culture (LCC) and air-interface culture (AIC) conditions have both been developed for the evaluation of aerosol anticancer therapeutics in solution and aerosols, respectively. The MCS were formed by seeding lung cancer cells on top of collagen where they formed spheroids due to the prevalence of cell-to-cell interactions. LCC MCS were exposed to paclitaxel (PTX) in media whereas AIC MCS were exposed to dry powder PEGylated phospholipid aerosol microparticles containing paclitaxel. The difference in viability for 2D versus 3D culture for both LCC and AIC was evaluated along with the effects of the particles on lung epithelium via transepithelial electrical resistance (TEER) measurements. For LCC and AIC conditions, the 3D spheroids were more resistant to treatment with higher IC50 values for A549 and H358 cell lines. TEER results initially indicated a decrease in resistance upon drug or particle exposure, however, these values increased over the course of several days indicating the ability of the cells to recover. Overall, these studies offer a comprehensive in vitro evaluation of aerosol particles used in the treatment of lung cancer while introducing a new method for culturing lung cancer MCS in both LCC and AIC conditions.
• Muralidharan, P., Hayes, D., Black, S. M., & Mansour, H. M. (2016). Microparticulate/Nanoparticulate Powders of a Novel Nrf2 Activator and an Aerosol Performance Enhancer for Pulmonary Delivery Targeting the Lung Nrf2/Keap-1 Pathway. Molecular systems design & engineering, 1(1), 48-65.
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  This systematic and comprehensive study reports for the first time on the successful rational design of advanced inhalable therapeutic dry powders containing dimethyl fumarate, a first-in-class Nrf2 activator drug to treat pulmonary inflammation, using particle engineering design technology for targeted delivery to the lungs as advanced spray dried (SD) one-component DPIs. In addition, two-component co-spray dried (co-SD) DMF:D-Man DPIs with high drug loading were successfully designed for targeted lung delivery as advanced DPIs using organic solution advanced spray drying in closed mode. Regional targeted deposition using design of experiments (DoE) for in vitro predictive lung modeling based on aerodynamic properties was tailored based on composition and spray drying parameters. These findings indicate the significant potential of using D-Man in spray drying to improve particle formation and aerosol performance of small molecule with a relatively low melting point. These respirable microparticles/nanoparticles in the solid-state exhibited excellent aerosol dispersion performance with an FDA-approved human DPI device. Using in vitro predictive lung deposition modeling, the aerosol deposition patterns of these particles show the capability to reach lower airways to treat inflammation in this region in pulmonary diseases such as acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), and pulmonary endothelial disease.
• de la Vega, M. R., Dodson, M., Gross, C., Mansour, H. M., Lantz, R. C., Chapman, E., Wang, T., Black, S. M., Garcia, J. G., & Zhang, D. D. (2016). Role of Nrf2 and Autophagy in Acute Lung Injury. Current pharmacology reports, 2(2), 91-101.
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  Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. Characterized by severe inflammation and compromised lung function, ALI/ARDS result in very high mortality of affected individuals. Currently, there are no effective treatments for ALI/ARDS, and ironically, therapies intended to aid patients (specifically mechanical ventilation, MV) may aggravate the symptoms. Key events contributing to the development of ALI/ARDS are: increased oxidative and proteotoxic stresses, unresolved inflammation, and compromised alveolar-capillary barrier function. Since the airways and lung tissues are constantly exposed to gaseous oxygen and airborne toxicants, the bronchial and alveolar epithelial cells are under higher oxidative stress than other tissues. Cellular protection against oxidative stress and xenobiotics is mainly conferred by Nrf2, a transcription factor that promotes the expression of genes that regulate oxidative stress, xenobiotic metabolism and excretion, inflammation, apoptosis, autophagy, and cellular bioenergetics. Numerous studies have demonstrated the importance of Nrf2 activation in the protection against ALI/ARDS, as pharmacological activation of Nrf2 prevents the occurrence or mitigates the severity of ALI/ARDS. Another promising new therapeutic strategy in the prevention and treatment of ALI/ARDS is the activation of autophagy, a bulk protein and organelle degradation pathway. In this review, we will discuss the strategy of concerted activation of Nrf2 and autophagy as a preventive and therapeutic intervention to ameliorate ALI/ARDS.
• Hayes, D., Black, S. M., Tobias, J. D., Mansour, H. M., & Whitson, B. A. (2015). Influence of pulmonary hypertension on survival in advanced lung disease. Lung [Impact Factor: 2.271], 193(2), 213-21.
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  Effects of pulmonary hypertension (PH) in advanced lung disease remain unclear.
• Hayes, D., Kirkby, S., Whitson, B. A., Black, S. M., Sheikh, S. I., Tobias, J. D., Mansour, H. M., & Kopp, B. T. (2015). Mortality Risk and Pulmonary Function in Adults With Cystic Fibrosis at Time of Wait Listing for Lung Transplantation. The Annals of thoracic surgery [Impact Factor: 3.849], 100(2), 474-9.
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  Lung transplantation (LTx) benefit for survival in cystic fibrosis (CF) patients placed on the wait list is not well studied.
• Hayes, D., Kopp, B. T., Tobias, J. D., Woodley, F. W., Mansour, H. M., Tumin, D., & Kirkby, S. E. (2015). Survival in Patients with Advanced Non-cystic Fibrosis Bronchiectasis Versus Cystic Fibrosis on the Waitlist for Lung Transplantation. Lung [Impact Factor: 2.271], 193(6), 933-8.
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  Survival in non-cystic fibrosis (CF) bronchiectasis is not well studied.
• Hayes, D., McCoy, K. S., Whitson, B. A., Mansour, H. M., & Tobias, J. D. (2015). High-risk age window for mortality in children with cystic fibrosis after lung transplantation. Pediatric transplantation [Impact Factor: 1.441, 19(2), 206-10.
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  LTx in children with CF remains controversial. The UNOS database was queried from 1987 to 2013 for CF patients
• Hayes, D., Patel, A. V., Black, S. M., McCoy, K. S., Kirkby, S., Tobias, J. D., Mansour, H. M., & Whitson, B. A. (2015). Influence of diabetes on survival in patients with cystic fibrosis before and after lung transplantation. The Journal of thoracic and cardiovascular surgery [Impact Factor: 4.168], 150(3), 707-13.e2.
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  The influence of diabetes mellitus (DM) on survival in patients with cystic fibrosis (CF) before and after lung transplantation is not well studied.
• Hayes, D., Tumin, D., Daniels, C. J., McCoy, K. S., Mansour, H. M., Tobias, J. D., & Kirkby, S. E. (2015). Pulmonary Artery Pressure and Benefit of Lung Transplantation in Adult Cystic Fibrosis Patients. The Annals of thoracic surgery [Impact Factor: 3.849].
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  The effect of lung transplantation (LTx) in patients afflicted with cystic fibrosis (CF) and pulmonary hypertension (PH) at placement on the waiting list is not well studied.
• Hayes, D., Whitson, B. A., Ghadiali, S. N., Lloyd, E. A., Tobias, J. D., Mansour, H. M., & Black, S. M. (2015). Survival in Adult Lung Transplant Recipients Receiving Pediatric Versus Adult Donor Allografts. The Annals of thoracic surgery, 100(4), 1211-6.
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  Recent evidence showed that pediatric donor lungs increased rates of allograft failure in adult lung transplant recipients; however, the influence on survival is unclear.
• Hayes, D., Whitson, B. A., Ghadiali, S. N., Tobias, J. D., Mansour, H. M., & Black, S. M. (2015). Influence of HLA Mismatching on Survival in Lung Transplantation. Lung [Impact Factor: 2.271], 193(5), 789-97.
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  Data on human leukocyte antigen (HLA) mismatching and survival after lung transplantation (LTx) are variable.
• Lu, Q., Harris, V. A., Kumar, S., Mansour, H. M., & Black, S. M. (2015). Autophagy in neonatal hypoxia ischemic brain is associated with oxidative stress. Redox biology, 6, 516-23.
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  Autophagy is activated when the neonatal brain exposed to hypoxia ischemia (HI), but the mechanisms underlying its activation and its role in the neuronal cell death associated with HI is unclear. We have previously shown that reactive oxygen species (ROS) derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase play an important role in HI-mediated neuronal cell death. Thus, the aim of this study was to determine if ROS is involved in the activation of autophagy in HI-mediated neonatal brain injury and to determine if this is a protective or deleterious pathway. Initial electron microscopy data demonstrated that autophagosome formation is elevated in P7 hippocampal slice cultures exposed to oxygen-glucose deprivation (OGD). This corresponded with increased levels of LC3II mRNA and protein. The autophagy inhibitor, 3-methyladenine (3-MA) effectively reduced LC3II levels and autophagosome formation in hippocampal slice cultures exposed to OGD. Neuronal cell death was significantly attenuated. Finally, we found that the pharmacologic inhibition of NADPH oxidase using apocynin or gp91ds-tat decreased autophagy in hippocampal slice cultures and the rat brain respectively. Thus, our results suggest that an activation of autophagy contributes to neonatal HI brain injury this is oxidative stress dependent.
• Mansour, H. (2015). Aerosol Medicine.. Pan European Networks: Science & Technology, 16, 1-2.
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  Aerosol Medicine. Pan European Networks: Science & Technology (2015) 16:1-2.
• Mansour, H. (2015). High-Precision Pulmonary Medicine.. International Innovation (Health & Nanomedicine), 185, 99-101.
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  5. High-Precision Pulmonary Medicine. International Innovation (2015) 185 (Health & Nanomedicine): 99-101.
• Mansour, H. (2015). Pulmonary Disease Research.. Adjacent Government, 80-81.
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  Pulmonary Disease Research. Adjacent Government (2015): 80-81
• Muralidharan, P., Hayes, D., & Mansour, H. M. (2015). Dry powder inhalers in COPD, lung inflammation and pulmonary infections. Expert opinion on drug delivery [Impact Factor: 4.840], 12(6), 947-62.
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  The number of pulmonary diseases that are effectively treated by aerosolized medicine continues to grow.
• Muralidharan, P., Malapit, M., Mallory, E., Hayes, D., & Mansour, H. M. (2015). Inhalable nanoparticulate powders for respiratory delivery. Nanomedicine : nanotechnology, biology, and medicine [Impact Factor: 6.155], 11(5), 1189-99.
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  Nanoparticles are extensively studied for drug delivery and are proving to be effective in drug delivery and the diagnostic field. Drug delivery to lungs has its advantages over other routes of administration. Inhalable powders consisting of nanoparticles are gaining much interest in respiratory research and clinical therapy. Particle engineering technique is a key factor to develop inhalable formulations that can successfully deliver drug with improved therapeutic effect and enhanced targeting. Inhalable nanoparticles in the solid-state dry powders for targeted pulmonary delivery offer unique advantages and are an exciting new area of research. Nasal delivery of inhalable nanoparticulate powders is gaining research attention recently, particularly in vaccine applications, systemic drug delivery in the treatment of pain, and non-invasive brain targeting. Fundamental aspects and recent advancements along with future prospects of inhalable powders consisting of nanoparticles in the solid-state for respiratory delivery are presented.
• Stocke, N. A., Meenach, S. A., Arnold, S. M., Mansour, H. M., & Hilt, J. Z. (2015). Formulation and characterization of inhalable magnetic nanocomposite microparticles (MnMs) for targeted pulmonary delivery via spray drying. International journal of pharmaceutics [Impact Factor: 3.650], 479(2), 320-8.
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  Targeted pulmonary delivery facilitates the direct application of bioactive materials to the lungs in a controlled manner and provides an exciting platform for targeting magnetic nanoparticles (MNPs) to the lungs. Iron oxide MNPs remotely heat in the presence of an alternating magnetic field (AMF) providing unique opportunities for therapeutic applications such as hyperthermia. In this study, spray drying was used to formulate magnetic nanocomposite microparticles (MnMs) consisting of iron oxide MNPs and d-mannitol. The physicochemical properties of these MnMs were evaluated and the in vitro aerosol dispersion performance of the dry powders was measured by the Next Generation Impactor(®). For all powders, the mass median aerosol diameter (MMAD) was 200W/g, and in vitro studies on a human lung cell line indicated moderate cytotoxicity of these materials. These inhalable composites present a class of materials with many potential applications and pose a promising approach for thermal treatment of the lungs through targeted pulmonary administration of MNPs.
• Hayes Jr., D., Adler, B., Turner, T. L., & Mansour, H. M. (2014). Alternative tacrolimus and sirolimus regimen associated with rapid resolution of posterior reversible encephalopathy syndrome after lung transplantation. Pediatric Neurology (Impact Factor: 1.504), 50(3), 272-275.
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  Abstract: Background Neurotoxicity is a significant complication of calcineurin inhibitor use, and posterior reversible encephalopathy syndrome has been reported. Limited data exist on the use of alternative immunosuppression regimens in the management of posterior reversible encephalopathy syndrome in transplant recipients. Methods We present the immunosuppression management strategy of a girl who underwent bilateral lung transplantation for cystic fibrosis 6 months earlier, then suddenly developed a grand mal seizure due to posterior reversible encephalopathy syndrome diagnosed by magnetic resonance imaging of the brain. In an effort to reduce her tacrolimus dose, an alternative immunosuppressant regimen combining tacrolimus and sirolimus was used. Results After the modification of her immunosuppressant regimen, there was rapid clinical improvement with no further seizures. Her brain findings had resolved on magnetic resonance imaging 2 months later. Over the next 6 months, allograft function remained stable and surveillance transbronchial biopsies found no allograft rejection on the combined sirolimus and tacrolimus therapy. Conclusions Tacrolimus-associated neurotoxicity resolved in a lung transplant recipient with a combined tacrolimus and sirolimus regimen. This combined therapy appears to be an effective alternative for lung transplant recipients that allow them to receive the benefits of both drugs but at lower doses, which reduces the risk for adverse effects. © 2014 Elsevier Inc. All rights reserved.
• Hayes, D., Tobias, J. D., Mansour, H. M., Kirkby, S., McCoy, K. S., Daniels, C. J., & Whitson, B. A. (2014). Pulmonary hypertension in cystic fibrosis with advanced lung disease. American journal of respiratory and critical care medicine (Impact Factor: 11.986), 190(8), 898-905.
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  The impact of pulmonary hypertension (PH) on survival in cystic fibrosis (CF) remains unclear.
• Hayes, D., Yates, A. R., Duffy, V. L., Tobias, J. D., Mansour, H. M., Olshove, V. F., & Preston, T. J. (2014). Rapid placement of bicaval dual-lumen catheter in a swine model of venovenous ECMO. Journal of investigative surgery : the official journal of the Academy of Surgical Research (Impact Factor: 1.316), 27(1), 27-31.
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  Venovenous (VV) extracorporeal membrane oxygenation (ECMO) applied through a single site with a bicaval dual-lumen (BCDL) catheter is a growing method of treatment of acute respiratory failure, thus animal models for research purposes are needed. We describe a rapid technique for the placement of the BCDL catheter for single-site VV ECMO in swine.
• Li, X., Vogt, F. G., Hayes, D., & Mansour, H. M. (2014). Design, characterization, and aerosol dispersion performance modeling of advanced co-spray dried antibiotics with mannitol as respirable microparticles/nanoparticles for targeted pulmonary delivery as dry powder inhalers. Journal of pharmaceutical sciences (Impact Factor: 3.007), 103(9), 2937-49.
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  Dry powder inhalation aerosols of antibiotic drugs (a first-line aminoglycoside, tobramycin, and a first-line macrolide, azithromycin) and a sugar alcohol mucolytic agent (mannitol) as co-spray dried (co-SD) particles at various molar ratios of drug:mannitol were successfully produced by organic solution advanced co-spray drying from dilute solute concentration. These microparticulate/nanoparticulate aerosols consisting of various antibiotic drug:mannitol molar ratios were rationally designed with a narrow and unimodal primary particle size distribution, spherical particle shape, relatively smooth particle surface, and very low residual water content to minimize the interparticulate interactions and enhance in vitro aerosolization. These microparticulate/nanoparticulate inhalation powders were high-performing aerosols as reflected in the aerosol dispersion performance parameters of emitted dose, fine particle fraction (FPF), respirable fraction (RF), and mass median aerodynamic diameter (MMAD). The glass transition temperature (Tg) values were significantly above room temperature, which indicated that the co-SD powders were all in the amorphous glassy state. The Tg values for co-SD tobramycin:mannitol powders were significantly lower than those for co-SD azithromycin:mannitol powders. The interplay between aerosol dispersion performance parameters and Tg was modeled where higher Tg values (i.e., more ordered glass) were correlated with higher values in FPF and RF and lower values in MMAD.
• Li, X., Vogt, F. G., Hayes, D., & Mansour, H. M. (2014). Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried microparticulate/nanoparticulate antibiotic dry powders of tobramycin and azithromycin for pulmonary inhalation aerosol delivery. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Impact Factor: 3.005), 52, 191-205.
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  The purpose of this study was to systematically design pure antibiotic drug dry powder inhalers (DPIs) for targeted antibiotic pulmonary delivery in the treatment of pulmonary infections and comprehensively correlate the physicochemical properties in the solid-state and spray-drying conditions effects on aerosol dispersion performance as dry powder inhalers (DPIs). The two rationally chosen model antibiotic drugs, tobramycin (TOB) and azithromycin (AZI), represent two different antibiotic drug classes of aminoglycosides and macrolides, respectively. The particle size distributions were narrow, unimodal, and in the microparticulate/nanoparticulate size range. The SD particles possessed relatively spherical particle morphology, smooth surface morphology, low residual water content, and the absence of long-range molecular order. The emitted dose (ED%), fine particle fraction (FPF%) and respirable fraction (RF%) were all excellent. The MMAD values were in the inhalable range (
• Meenach, S. A., Anderson, K. W., Hilt, J. Z., McGarry, R. C., & Mansour, H. M. (2014). High-performing dry powder inhalers of paclitaxel DPPC/DPPG lung surfactant-mimic multifunctional particles in lung cancer: physicochemical characterization, in vitro aerosol dispersion, and cellular studies. AAPS PharmSciTech (Impact Factor: 1.776), 15(6), 1574-87.
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  Inhalable lung surfactant-based carriers composed of synthetic phospholipids, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG), along with paclitaxel (PTX), were designed and optimized as respirable dry powders using organic solution co-spray-drying particle engineering design. These materials can be used to deliver and treat a wide variety of pulmonary diseases with this current work focusing on lung cancer. In particular, this is the first time dry powder lung surfactant-based particles have been developed and characterized for this purpose. Comprehensive physicochemical characterization was carried out to analyze the particle morphology, surface structure, solid-state transitions, amorphous character, residual water content, and phospholipid bilayer structure. The particle chemical composition was confirmed using attenuated total reflectance-Fourier-transform infrared (ATR-FTIR) spectroscopy. PTX loading was high, as quantified using UV-VIS spectroscopy, and sustained PTX release was measured over weeks. In vitro cellular characterization on lung cancer cells demonstrated the enhanced chemotherapeutic cytotoxic activity of paclitaxel from co-spray-dried DPPC/DPPG (co-SD DPPC/DPPG) lung surfactant-based carrier particles and the cytotoxicity of the particles via pulmonary cell viability analysis, fluorescent microscopy imaging, and transepithelial electrical resistance (TEER) testing at air-interface conditions. In vitro aerosol performance using a Next Generation Impactor™ (NGI™) showed measurable powder deposition on all stages of the NGI and was relatively high on the lower stages (nanometer aerodynamic size). Aerosol dispersion analysis of these high-performing DPIs showed mass median diameters (MMADs) that ranged from 1.9 to 2.3 μm with excellent aerosol dispersion performance as exemplified by high values of emitted dose, fine particle fractions, and respirable fractions.
• Muralidharan, P., Mallory, E., Malapit, M., Hayes, D., & Mansour, H. M. (2014). Inhalable PEGylated Phospholipid Nanocarriers and PEGylated Therapeutics for Respiratory Delivery as Aerosolized Colloidal Dispersions and Dry Powder Inhalers. Pharmaceutics, 6(2), 333-53.
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  Nanomedicine is making groundbreaking achievements in drug delivery. The versatility of nanoparticles has given rise to its use in respiratory delivery that includes inhalation aerosol delivery by the nasal route and the pulmonary route. Due to the unique features of the respiratory route, research in exploring the respiratory route for delivery of poorly absorbed and systemically unstable drugs has been increasing. The respiratory route has been successfully used for the delivery of macromolecules like proteins, peptides, and vaccines, and continues to be examined for use with small molecules, DNA, siRNA, and gene therapy. Phospholipid nanocarriers are an attractive drug delivery system for inhalation aerosol delivery in particular. Protecting these phospholipid nanocarriers from pulmonary immune system attack by surface modification by polyethylene glycol (PEG)ylation, enhancing mucopenetration by PEGylation, and sustaining drug release for controlled drug delivery are some of the advantages of PEGylated liposomal and proliposomal inhalation aerosol delivery. This review discusses the advantages of using PEGylated phospholipid nanocarriers and PEGylated therapeutics for respiratory delivery through the nasal and pulmonary routes as inhalation aerosols.
• Xiaojian, L. i., Vogt, F. G., Hayes, D., & Mansour, H. M. (2014). Design, characterization, and aerosol dispersion performance modeling of advanced spray-dried microparticulate/nanoparticulate mannitol powders for targeted pulmonary delivery as dry Powder inhalers. Journal of Aerosol Medicine and Pulmonary Drug Delivery (Impact Factor: 2.395), 27(2), 81-93.
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  Abstract: Background: The purpose was to design and characterize inhalable microparticulate/nanoparticulate dry powders of mannitol with essential particle properties for targeted dry powder delivery for cystic fibrosis mucolytic treatment by dilute organic solution spray drying, and, in addition, to tailor and correlate aerosol dispersion performance delivered as dry powder inhalers based on spray-drying conditions and solid-state physicochemical properties. Methods: Organic solution advanced spray drying from dilute solution followed by comprehensive solid-state physicochemical characterization and in vitro dry powder aerosolization were used. Results: The particle size distribution of the spray-dried (SD) powders was narrow, unimodal, and in the range of ∼500nm to 2.0μm. The particles possessed spherical particle morphology, relatively smooth surface morphology, low water content and vapor sorption (crystallization occurred at exposure above 65% relative humidity), and retention of crystallinity by polymorphic interconversion. The emitted dose, fine particle fraction (FPF), and respirable fraction (RF) were all relatively high. The mass median aerodynamic diameters were below 4μm for all SD mannitol aerosols. Conclusion: The in vitro aerosol deposition stage patterns could be tailored based on spray-drying pump rate. Positive linear correlation was observed between both FPF and RF values with spray-drying pump rates. The interplay between various spray-drying conditions, particle physicochemical properties, and aerosol dispersion performance was observed and examined, which enabled tailoring and modeling of high aerosol deposition patterns.© Mary Ann Liebert, Inc.
• Duan, J., Vogt, F. G., Xiaojian, L. i., Hayes, D., & Mansour, H. M. (2013). Design, characterization, and aerosolization of organic solution advanced spray-dried moxifloxacin and ofloxacin dipalmitoylphosphatidylcholine (DPPC) microparticulate/nanoparticulate powders for pulmonary inhalation aerosol delivery. International journal of nanomedicine (Impact Factor: 4.195), 8, 3489-3505.
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  PMID: 24092972;PMCID: PMC3787929;Abstract: The aim of this study was to design and develop respirable antibiotics moxifloxacin (MOXI) hydrochloride and ofloxacin (OFLX) microparticles and nanoparticles, and multifunctional antibiotics particles with or without lung surfactant 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced by advanced spray-drying particle engineering from an organic solution in closed mode (no water) from dilute solution. Scanning electron microscopy indicated that these particles had both optimal particle morphology and surface morphology, and the particle size distributions were suitable for pulmonary delivery. Comprehensive and systematic physicochemical characterization and in vitro aerosol dispersion performance revealed significant differences between these two fluoroquinolone antibiotics following spray drying as drug aerosols and as cospray-dried antibiotic drug: DPPC aerosols. Fourier transform infrared spectroscopy and confocal Raman microspectroscopy were employed to probe composition and interactions in the solid state. Spray-dried MOXI was rendered noncrystalline (amorphous) following organic solution advanced spray drying. This was in contrast to spray-dried OFLX, which retained partial crystallinity, as did OFLX:DPPC powders at certain compositions. Aerosol dispersion performance was conducted using inertial impaction with a dry powder inhaler device approved for human use. The present study demonstrates that the use of DPPC offers improved aerosol delivery of MOXI as cospray-dried microparticulate/ nanoparticulate powders, whereas residual partial crystallinity influenced aerosol dispersion of OFLX and most of the compositions of OFLX:DPPC inhalation powders. © 2013 Duan et al.
• Hayes Jr., D., Baker, P. B., Mansour, H. M., Peeples, M. E., & Nicol, K. K. (2013). Interstitial lung disease in a child with antisynthetase syndrome. Lung (Impact Factor: 2.171), 191(4), 441-443.
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  PMID: 23652349;Abstract: Introduction: Antisynthetase Syndrome is associated with interstitial lung disease in adult patients, but this has not been described in children. Materials and methods: A 13-year-old with interstitial lung disease due to Antisynthetase Syndrome and pulmonary arterial hypertension underwent emergent bilateral lung transplantation after a rapid clinical decline. Conclusion: We present the clinical, radiographic, and histological findings of a child with interstitial lung disease due to Antisynthetase Syndrome. © 2013 Springer Science+Business Media New York.
• Hayes Jr., D., Daniels, C. J., Mansour, H. M., Kopp, B. T., Yates, A. R., McCoy, K. S., Patel, A. V., & Kirkby, S. (2013). Right heart catheterization measuring central hemodynamics in cystic fibrosis during exercise. Respiratory Medicine (Impact Factor: 2.917), 107(9), 1365-1369.
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  PMID: 23830093;Abstract: Background Although pulmonary arterial hypertension (PAH) is a potential co-morbidity in cystic fibrosis (CF), right heart catheterization (RHC) is not commonly performed in this patient population until referral for lung transplantation. Material and methods An non-randomized observational pilot study was performed after an exercise protocol with an upright stationary bicycle was added to RHC performed in patients with CF undergoing evaluation for lung transplantation (LT). Results Twelve consecutive patients with advanced lung disease due to CF referred for LT completed RHC with exercise protocol. Transthoracic echocardiography (TTE) prior to the RHC did not identify evidence of PAH or significant structural abnormalities; right and left ventricular systolic function were normal. non-randomized RHC in this same cohort found 75% (9/12) had PAH with an elevation of the mean pulmonary artery pressure (PAP) at rest with a mean (±SD) of 27.8 ± 4.9 mmHg that significantly increased during exercise to 47.2 ± 5.4 mmHg, p = 0.0025. For the last 6 patients, pulmonary vascular resistance was calculated during exercise, with a significant increase from 3.15 ± 0.3 to 12.8 ± 0.6 Wood Units (p = 0.0313) comparing measurements at rest to exercise. Conclusion RHC at rest and during exercise was safely and effectively performed in patients with CF referred for LT. Furthermore, central hemodynamic measurements found significant worsening of PAH during exercise in a small cohort of CF patients with advanced lung disease. © 2013 Elsevier Ltd. All rights reserved.
• Hayes Jr., D., Galantowicz, M., Yates, A. R., Preston, T. J., Mansour, H. M., & McConnell, P. I. (2013). Venovenous ECMO as a bridge to lung transplant and a protective strategy for subsequent primary graft dysfunction. Journal of Artificial Organs (Impact Factor: 1.60), 16(3), 382-385.
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  PMID: 23508264;Abstract: Extracorporeal membrane oxygenation (ECMO) is an established therapy for primary graft dysfunction (PGD) in adults after lung transplant, while venovenous (VV) ECMO is an evolving therapy that can bridge patients to lung transplantation. This report describes a case of relatively quick improvement of grade 3 PGD, based on the PaO2/FIO2 (P/F) ratio, in a 17-year-old patient with cystic fibrosis who was bridged to lung transplantation with ambulatory VV ECMO and then received support with VV ECMO as a protective strategy during the initial phases of PGD after lung transplantation. © 2013 The Japanese Society for Artificial Organs.
• Hayes Jr., D., Nicol, K. K., Tobias, J. D., Chicoine, L. G., Duffy, V. L., Mansour, H. M., & Preston, T. J. (2013). Identification of the nodose ganglia and TRPV1 in swine. Lung (Impact Factor: 2.171), 191(5), 445-457.
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  PMID: 23892914;
• Hayes, D., Kirkby, S., Mccoy, K. S., Mansour, H. M., Khosravi, M., Strawbridge, H., & Tobias, J. D. (2013). Reduction of lipid-laden macrophage index after laparoscopic Nissen fundoplication in cystic fibrosis patients after lung transplantation. Clinical Transplantation (Impact Factor: 1.486), 27(1), 121-125.
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  PMID: 23004684;Abstract: Background: Lipid-laden macrophage (LLM) index could be potentially useful in assessing gastroesophageal (GE) reflux and aspiration after lung transplantation (LT) in patients with cystic fibrosis (CF). Methods: A retrospective review of CF patients undergoing LT and/or laparoscopic Nissen fundoplication (LNF) from January 1, 2009, to December 31, 2011, was performed. Results: Seventeen CF patients (nine women), mean (±SD) age 27.9 ± 7.5 yr, underwent LT with mean (±SD) pre-transplant FEV1 of 20.9 ± 5.0% predicted. Seventy percentage (12/17) of patients underwent LNF without complications within 1-2 wk of LT. After LT, but prior to antireflux surgery, there was no significant difference in the mean (±SD) baseline LLM index (154 ± 41 vs. 146 ± 51, p = NS) between patients who were to undergo LNF and patients who did not. After LNF, a significant reduction in the mean (±SD) LLM index occurred following the procedure (154 ± 41-74 ± 54, p 
• Meenach, S. A., Anderson, K. W., Hilt, J. Z., McGarry, R. C., & Mansour, H. M. (2013). Characterization and aerosol dispersion performance of advanced spray-dried chemotherapeutic PEGylated phospholipid particles for dry powder inhalation delivery in lung cancer. European Journal of Pharmaceutical Sciences (Impact Factor: 3.005), 49(4), 699-711.
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  PMID: 23707466;Abstract: Pulmonary inhalation chemotherapeutic drug delivery offers many advantages for lung cancer patients in comparison to conventional systemic chemotherapy. Inhalable particles are advantageous in their ability to deliver drug deep in the lung by utilizing optimally sized particles and higher local drug dose delivery. In this work, spray-dried and co-spray dried inhalable lung surfactant-mimic PEGylated lipopolymers as microparticulate/nanoparticulate dry powders containing paclitaxel were rationally designed via organic solution advanced spray drying (no water) in closed-mode from dilute concentration feed solution. Dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) with varying PEG chain length were mixed with varying amounts of paclitaxel in methanol to produce co-spray dried microparticles and nanoparticles. Scanning electron microscopy showed the spherical particle morphology of the inhalable particles. Thermal analysis and X-ray powder diffraction confirmed the retention of the phospholipid bilayer structure in the solid-state following spray drying, the degree of solid-state molecular order, and solid-state phase transition behavior. The residual water content of the particles was very low as quantified analytically Karl Fisher titration. The amount of paclitaxel loaded into the particles was quantified which indicated high encapsulation efficiencies (43-99%). Dry powder aerosol dispersion performance was measured in vitro using the Next Generation Impactor™ (NGI™) coupled with the Handihaler® dry powder inhaler device and showed mass median aerodynamic diameters in the range of 3.4-7 lm. These results demonstrate that this novel microparticulate/nanoparticulate chemotherapeutic PEGylated phospholipid dry powder inhalation aerosol platform has great potential in lung cancer drug delivery. © 2013 Elsevier B.V.
• Meenach, S. A., Vogt, F. G., Anderson, K. W., Hilt, J. Z., McGarry, R. C., & Mansour, H. M. (2013). Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols. International Journal of Nanomedicine (Impact Factor: 4.195), 8, 275-293.
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  PMID: 23355776;PMCID: PMC3552552;Abstract: Novel advanced spray-dried and co-spray-dried inhalable lung surfactant-mimic phospholipid and poly(ethylene glycol) (PEG)ylated lipopolymers as microparticulate/ nanoparticulate dry powders of biodegradable biocompatible lipopolymers were rationally formulated via an organic solution advanced spray-drying process in closed mode using various phospholipid formulations and rationally chosen spray-drying pump rates. Ratios of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine PEG (DPPE-PEG) with varying PEG lengths were mixed in a dilute methanol solution. Scanning electron microscopy images showed the smooth, spherical particle morphology of the inhalable particles. The size of the particles was statistically analyzed using the scanning electron micrographs and SigmaScan® software and were determined to be 600nm to 1.2μm in diameter, which is optimal for deep-lung alveolar penetration. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) were performed to analyze solid-state transitions and long-range molecular order, respectively, and allowed for the confirmation of the presence of phospholipid bilayers in the solid state of the particles. The residual water content of the particles was very low, as quantified analytically via Karl Fischer titration. The composition of the particles was confirmed using attenuated total-reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy and confocal Raman microscopy (CRM), and chemical imaging confirmed the chemical homogeneity of the particles. The dry powder aerosol dispersion properties were evaluated using the Next Generation Impactor™ (NGI™) coupled with the HandiHaler® dry powder inhaler device, where the mass median aerodynamic diameter from 2.6 to 4.3 μm with excellent aerosol dispersion performance, as exemplified by high values of emitted dose, fine particle fraction, and respirable fraction. Overall, it was determined that the pump rates defined in the spray-drying process had a significant effect on the solid-state particle properties and that a higher pump rate produced the most optimal system. Advanced dry powder inhalers of inhalable lipopolymers for targeted dry powder inhalation delivery were successfully achieved. © 2013 Meenach etal, publisher and licensee Dove Medical Press Ltd.
• Park, C., Xiaojian, L. i., Vogt, F. G., Hayes Jr., D., Zwischenberger, J. B., Park, E., & Mansour, H. M. (2013). Advanced spray-dried design, physicochemical characterization, and aerosol dispersion performance of vancomycin and clarithromycin multifunctional controlled release particles for targeted respiratory delivery as dry powder inhalation aerosols. International Journal of Pharmaceutics (Impact Factor: 3.785), 455(1-2), 374-392.
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  PMID: 23820131;Abstract: Respirable microparticles/nanoparticles of the antibiotics vancomycin (VCM) and clarithromycin (CLM) were successfully designed and developed by novel organic solution advanced spray drying from methanol solution. Formulation optimization was achieved through statistical experimental design of pump feeding rates of 25% (Low P), 50% (Medium P) and 75% (High P). Systematic and comprehensive physicochemical characterization and imaging were carried out using scanning electron microscopy (SEM), hot-stage microscopy (HSM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Karl Fischer titration (KFT), laser size diffraction (LSD), gravimetric vapor sorption (GVS), confocal Raman microscopy (CRM) and spectroscopy for chemical imaging mapping. These novel spray-dried (SD) microparticulate/nanoparticulate dry powders displayed excellent aerosol dispersion performance as dry powder inhalers (DPIs) with high values in emitted dose (ED), respirable fraction (RF), and fine particle fraction (FPF). VCM DPIs displayed better aerosol dispersion performance compared to CLM DPIs which was related to differences in the physicochemical and particle properties of VCM and CLM. In addition, organic solution advanced co-spray drying particle engineering design was employed to successfully produce co-spray-dried (co-SD) multifunctional microparticulate/ nanoparticulate aerosol powder formulations of VCM and CLM with the essential lung surfactant phospholipid, dipalmitoylphosphatidylcholine (DPPC), for controlled release pulmonary nanomedicine delivery as inhalable dry powder aerosols. Formulation optimization was achieved through statistical experimental design of molar ratios of co-SD VCM:DPPC and co-SD CLM:DPPC. XRPD and DSC confirmed that the phospholipid bilayer structure in the solid-state was preserved following spray drying. Co-SD VCM:DPPC and co-SD CLM:DPPC dry powder aerosols demonstrated controlled release of antibiotic drug that was fitted to various controlled release mathematical fitting models. The Korsmeyer-Peppas model described the best data fit for all powders suggesting super case-II transport mechanism of controlled release. Excellent aerosol dispersion performance for all co-SD microparticulate/nanoparticulate DPIs was higher than the SD antibiotic drugs suggesting that DPPC acts as an aerosol performance enhancer for these antibiotic aerosol dry powders. Co-SD VCM:DPPC DPIs had higher aerosol dispersion parameters compared to co-SD CLM:DPPC which was related to differences in the physicochemical properties of VCM and CLM. © 2013 Elsevier B.V. All rights reserved.
• Xiao, W. u., Hayes Jr, D., Zwischenberger, J. B., Kuhn, R. J., & Mansour, H. M. (2013). Design and physicochemical characterization of advanced spray-dried tacrolimus multifunctional particles for inhalation. Drug Design, Development and Therapy (Impact Factor: 3.026), 7, 59-72.
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  PMID: 23403805;PMCID: PMC3569053;Abstract: The aim of this study was to design, develop, and optimize respirable tacrolimus microparticles and nanoparticles and multifunctional tacrolimus lung surfactant mimic particles for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced at different pump rates by advanced spray-drying particle engineering design from organic solution in closed mode. In addition, multifunctional tacrolimus lung surfactant mimic dry powder particles were prepared by co-dissolving tacrolimus and lung surfactant mimic phospholipids in methanol, followed by advanced co-spray-drying particle engineering design technology in closed mode. The lung surfactant mimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-[phosphor-rac-1-glycerol]. Laser diffraction particle sizing indicated that the particle size distributions were suitable for pulmonary delivery, whereas scanning electron microscopy imaging indicated that these particles had both optimal particle morphology and surface morphology. Increasing the pump rate percent of tacrolimus solution resulted in a larger particle size. X-ray powder diffraction patterns and differential scanning calorimetry thermograms indicated that spray drying produced particles with higher amounts of amorphous phase. X-ray powder diffraction and differential scanning calorimetry also confirmed the preservation of the phospholipid bilayer structure in the solid state for all engineered respirable particles. Furthermore, it was observed in hot-stage micrographs that raw tacrolimus displayed a liquid crystal transition following the main phase transition, which is consistent with its interfacial properties. Water vapor uptake and lyotropic phase transitions in the solid state at varying levels of relative humidity were determined by gravimetric vapor sorption technique. Water content in the various powders was very low and well within the levels necessary for dry powder inhalation, as quantified by Karl Fisher coulometric titration. Conclusively, advanced spray-drying particle engineering design from organic solution in closed mode was successfully used to design and optimize solid-state particles in the respirable size range necessary for targeted pulmonary delivery, particularly for the deep lung. These particles were dry, stable, and had optimal properties for dry powder inhalation as a novel pulmonary nanomedicine. © 2013 Wu et al.
• Xiao, W. u., Zhang, W., Hayes Jr., D., & Mansour, H. M. (2013). Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried cyclosporine A multifunctional particles for dry powder inhalation aerosol delivery. International Journal of Nanomedicine (Impact Factor: 4.195), 8, 1269-1283.
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  PMID: 23569375;PMCID: PMC3615928;Abstract: In this systematic and comprehensive study, inhalation powders of the polypeptide immunosuppressant drug - cyclosporine A - for lung delivery as dry powder inhalers (DPIs) were successfully designed, developed, and optimized. Several spray drying pump rates were rationally chosen. Comprehensive physicochemical characterization and imaging was carried out using scanning electron microscopy, hot-stage microscopy, differential scanning calorimetry, powder X-ray diffraction, Karl Fischer titration, laser size diffraction, and gravimetric vapor sorption. Aerosol dispersion performance was conducted using a next generation impactor with a Food and Drug Administration-approved DPI device. These DPIs displayed excellent aerosol dispersion performance with high values in emitted dose, respirable fraction, and fine particle fraction. In addition, novel multifunctional inhalation aerosol powder formulations of cyclosporine A with lung surfactant-mimic phospholipids were also successfully designed and developed by advanced organic solution cospray drying in closed mode. The lung surfactant-mimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-(phosphor-rac-1-glycerol). These cyclosporine A lung surfactant-mimic aerosol powder formulations were comprehensively characterized. Powder X-ray diffraction and differential scanning calorimetry confirmed that the phospholipid bilayer structure in the solid state was preserved following advanced organic solution spray drying in closed mode. These novel multifunctional inhalation powders were optimized for DPI delivery with excellent aerosol dispersion performance and high aerosol performance parameters. © 2013 Wu et al, publisher and licensee Dove Medical Press Ltd.
• Zheng, Z., Zhang, W., Sun, W., Xiaojian, L. i., Duan, J., Cui, J., Feng, Z., & Mansour, H. M. (2013). Influence of the carboxymethyl chitosan anti-adhesion solution on the TGF-β1 in a postoperative peritoneal adhesion rat. Journal of Materials Science: Materials in Medicine (Impact Factor: 2.305), 24(11), 2549-2559.
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  PMID: 23820936;Abstract: The aim of this paper was to investigate the effect of carboxymethyl chitosan anti-adhesion solution on prevention of postsurgical adhesion. Forty adult male Wistar rats were randomly divided into three groups: 0.9 % normal saline solution (group A), hyaluronic acid gels (group B) and carboxymethyl chitosan anti-adhesion solution (group C). The animals were treated with normal saline, hyaluronic acid gels or carboxymethyl chitosan anti-adhesion solution at the time of surgery. After 2 or 3 weeks, the degree of adhesions and histological effects were determined. The adhesions in groups B and C were significantly decreased, and the levels of TGF-β1 and hydroxyproline in group C were significantly lower than that in group A (P < 0.05). The histopathology in group C showed fewer inflammatory cells and fibroblasts. Carboxymethyl chitosan anti-adhesion solution can effectively prevent postoperative adhesion which is a promising drug delivery system in the context of postsurgical anti-adhesion. © 2013 Springer Science+Business Media New York.
• Duan, J., Mansour, H. M., Zhang, Y., Deng, X., Chen, Y., Wang, J., Pan, Y., & Zhao, J. (2012). Reversion of multidrug resistance by co-encapsulation of doxorubicin and curcumin in chitosan/poly(butyl cyanoacrylate) nanoparticles. International Journal of Pharmaceutics (Impact Factor: 3.785), 426(1-2), 193-201.
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  PMID: 22274587;Abstract: Co-encapsulated doxorubicin (DOX) and curcumin (CUR) in poly(butyl cyanoacrylate) nanoparticles (PBCA-NPs) were prepared with emulsion polymerization and interfacial polymerization. The mean particle size and mean zeta potential of CUR-DOX-PBCA-NPs were 133 ± 5.34 nm in diameter and +32.23 ± 4.56 mV, respectively. The entrapment efficiencies of doxorubicin and curcumin were 49.98 ± 3.32% and 94.52 ± 3.14%, respectively. Anticancer activities and reversal efficacy of the formulations and various combination approaches were assessed using 3-[4,5-dimethylthiazol-2- yl] 2,5-diphenyltetrazolium bromide assay and western blotting. The results showed that the dual-agent loaded PBCA-NPs system had the similar cytotoxicity to co-administration of two single-agent loaded PBCA-NPs (DOX-PBCA-NPs + CUR-PBCA-NPs), which was slightly higher than that of the free drug combination (DOX + CUR) and one free drug/another agent loaded PBCA-NPs combination (DOX + CUR-PBCA-NPs or CUR + DOX-PBCA-NPs). The simultaneous administration of doxorubicin and curcumin achieved the highest reversal efficacy and down-regulation of P-glycoprotein in MCF-7/ADR cell lines, an MCF-7 breast carcer cell line resistant to adriamycin. Multidrug resistance can be enhanced by combination delivery of encapsulated cytotoxic drugs and reversal agents. © 2012 Elsevier B.V. All rights reserved.
• Hayes Jr., D., & Mansour, H. M. (2012). Vanishing bronchus intermedius syndrome in a pediatric patient with cystic fibrosis after lung transplantation. Pediatric Transplantation (Impact Factor: 1.630), 16(8), E333-E337.
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  PMID: 22489792;Abstract: Airway complications occur frequently after lung transplantation. Bronchial stenosis is the most frequently encountered complication with the most severe form of that being the vanishing bronchus intermedius syndrome (VBIS). This rare disorder has never been reported in the pediatric population. This is the first report of VBIS in a pediatric patient, specifically a 16-yr-old male patient with cystic fibrosis whose course was complicated by a lower airway infection with Aspergillus fumigatus. The VBIS responded to bronchoscopic balloon dilation and placement of an airway stent. © 2012 John Wiley & Sons A/S.
• Hayes Jr., D., Winkler, M. A., Kirkby, S., Capasso, P., Mansour, H. M., & Attili, A. K. (2012). Preprocedural planning with prospectively triggered multidetector row CT angiography prior to bronchial artery embolization in cystic fibrosis patients with massive hemoptysis. Lung (Impact Factor: 2.171), 190(2), 221-225.
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  PMID: 22037830;Abstract: Study Objectives: The aim of this study was to determine if electrocardiographically synchronized, prospectively triggered multidetector row computed tomography (ECG-MDR-CT) angiography of the aorta can accurately predict the location of ectopic bronchial arteries in patients with cystic fibrosis (CF) with massive hemoptysis prior to bronchial artery embolization (BAE). Design and Setting: The study was a prospective, observational study from September 1, 2009 to June 30, 2011, conducted at a university hospital with an adult CF center. Patients The study included adult CF patients with massive hemoptysis. Results: A total of four adult patients (mean [± SD] age = 31.5 ± 7.9 years) with CF and massive hemoptysis underwent ECG-MDR-CT angiography. The location of the bleeding source was predicted in each case based on lung pathology observed on ECG-MDR-CT angiography. All four patients eventually required BAE without the need for conventional aortograms since the locations of the bronchial arteries were determined prior to the procedure. Review of lung pathology and arterial networks from the ECG-MDR-CT angiography data limited the number of selective catheterizations necessary to complete the procedures. BAE resulted in complete resolution of hemoptysis in three patients and successful mitigation of the bleeding in the fourth patient until lung transplantation was performed 1 week later. Conclusions: ECG-MDR-CT angiography accurately depicted bronchial artery anatomy in CF patients with massive hemoptysis and provided excellent preprocedural planning for BAE. The information provided by ECG-MDR-CT angiography of the aorta prior to conventional angiography decreased the BAE radiation dose and contrast volume and likely reduced table time. © Springer Science+Business Media, LLC 2011.
• Hayes, D., Mansour, H. M., Kirkby, S., & Phillips, A. B. (2012). Rapid acute onset of bronchiolitis obliterans syndrome in a lung transplant recipient after respiratory syncytial virus infection. Transplant Infectious Disease (Impact Factor: 2.25), 14(5), 548-550.
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  PMID: 22650803;Abstract: Bronchiolitis obliterans syndrome (BOS) can have either an acute or chronic onset with an abrupt or insidious course. The diagnosis is typically achieved by physiological criteria with development of a sustained decline in expiratory flow rates for at least 3 weeks. We review the rapid development of acute BOS and bronchiectasis after respiratory syncytial virus infection in a lung transplant recipient, who had been doing well with normal pulmonary function for 3 years after lung transplantation. © 2012 John Wiley & Sons A/S.
• Park, C., Mansour, H. M., Oh, T., Kim, J., Ha, J., Lee, B., Chi, S., Rhee, Y., & Park, E. (2012). Phase behavior of itraconazole-phenol mixtures and its pharmaceutical applications. International Journal of Pharmaceutics (Impact Factor: 3.785), 436(1-2), 652-658.
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  PMID: 22871560;Abstract: The aims of this study were to examine the phase behavior of itraconazole-phenol mixtures and assess the feasibility of topical formulations of itraconazole using eutectic mixture systems. Itraconazole-phenol eutectic mixtures were characterized using differential scanning calorimetry, Fourier transform infrared spectroscopy, 1H-nuclear magnetic resonance, and powder X-ray diffractometry. The skin permeation rates of itraconazole-phenol eutectic formulations were determined using Franz diffusion cells fitted with excised hairless mouse skins. Itraconazole can form eutectic compounds with phenol, and the hydrogen-bonding interactions between the carbonyl group in the itraconazole and hydroxyl group in phenol play a major role in itraconazole-phenol eutectic formation. Despite its high molecular weight and hydrophobicity, the drug (i.e.; itraconazole) can be permeated through excised hairless mouse skins from itraconazole-phenol eutectic formulations. The findings of this study emphasize the capabilities of the topical application of itraconazole via external preparations. © 2012 Elsevier B.V. All rights reserved.
• Park, C., Rhee, Y., Vogt, F. G., Hayes, D., Zwischenberger, J. B., DeLuca, P. P., & Mansour, H. M. (2012). Advances in microscopy and complementary imaging techniques to assess the fate of drugs ex vivo in respiratory drug delivery. An invited paper. Advanced Drug Delivery Reviews (Impact Factor: 12.707), 64(4), 344-356.
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  PMID: 21920394;Abstract: The technical advances in microscopy imaging techniques have been applied to assess the fate of drugs for researching respiratory drug delivery in ex vivo and in vivo experiments. Recent developments in optical imaging (confocal microscopy, multi-photon microscopy, fluorescence imaging (FLI) and bioluminescence imaging (BLI)), and in non-optical imaging (magnetic resonance imaging (MRI), computing tomography (CT), positron-emission tomography (PET) and single-photon-emission computed tomography (SPECT)) are presented with their derivative medical devices. Novel microscopy have been utilized to address many biological questions in basic research and are becoming powerful clinical tools for non-invasive objective diagnosis, guided treatment, and monitoring therapies. The goal of this paper is to present recent advances in microscopy imaging techniques and to discuss their novel applications in respiratory drug delivery imaging. © 2011 Elsevier B.V.
• Willis, L., Hayes Jr., D., & Mansour, H. M. (2012). Therapeutic liposomal dry powder inhalation aerosols for targeted lung delivery. Lung (Impact Factor: 2.171), 190(3), 251-262.
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  PMID: 22274758;Abstract: Therapeutic liposomal powders (i.e., lipospheres and proliposomes) for dry powder inhalation aerosol delivery, formulated with phospholipids similar to endogenous lung surfactant, offer unique opportunities in pulmonary nanomedicine while offering controlled release and enhanced stability. Many pulmonary diseases such as lung cancer, tuberculosis (TB), cystic fibrosis (CF), bacterial and fungal lung infections, asthma, and chronic obstructive pulmonary disease (COPD) could greatly benefit from this type of pulmonary nanomedicine approach that can be delivered in a targeted manner by dry powder inhalers (DPIs). These delivery systems may require smaller doses for efficacy, exhibit reduced toxicity, fewer side effects, controlled drug release over a prolonged time period, and increased formulation stability as inhaled powders. This state-of-the-art review presents these novel aspects in depth. © Springer Science+Business Media, LLC 2012.
• Hayes Jr., D., & Mansour, H. M. (2011). Improved outcomes of patients with end-stage cystic fibrosis requiring invasive mechanical ventilation for acute respiratory failure. Lung, 189(5), 409-415.
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  PMID: 21805164;Abstract: Study Objectives The aim of this study was to determine the effects of an antibiotic strategy with intravenous (IV) continuous infusion of a β-lactam (CIBL) antibiotic and high-dose extended-interval (HDEI) tobramycin upon outcomes in patients with cystic fibrosis (CF) requiring invasive mechanical ventilation (IMV) for acute respiratory failure. Design The study was a retrospective review from June 1, 2006, to December 1, 2010, of patients at a university hospital with an adult CF center. Results The study population included adult CF patients requiring IMV. A total of 15 hospitalizations with IMV episodes were reviewed, involving 10 adult (31.4±11.1 years) CF patients with end-stage lung disease (FEV 1 = 23.6±7.8% predicted) and malnutrition (body mass index = 20.5±3.1). Each patient survived to discharge and to follow-up 6 months later without the need for lung transplantation during the study period. Conclusions A novel antibiotic strategy with a CIBL antibiotic and HDEI tobramycin improved survival in a small cohort of critically ill CF patients with end-stage lung disease and malnutrition requiring IMV. © Springer Science+Business Media, LLC 2011.
• Hayes Jr., D., Ball, A. M., Mansour, H. M., Martin, C. A., & Flynn, J. D. (2011). Fungal infection in heart-lung transplant recipients receiving single-agent prophylaxis with itraconazole. Experimental and Clinical Transplantation (Impact Factor: 0.798), 9(6), 399-404.
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  PMID: 22142048;Abstract: Objectives: Heart and lung transplant recipients are at risk for invasive fungal infections. This study evaluated the affect of single-agent antifungal prophylaxis with itraconazole on the rate of fungal infections after heart or lung transplant. Materials and Methods: An observational, retrospective study was performed to evaluate the rate of fungal infections in heart and lung transplant recipients at the University of Kentucky Medical Center over 4.5 years who received itraconazole as a single therapy prophylaxis. Results: Eighty-three recipients (42 heart, 41 lung) had an overall fungal infection incidence of 16.9% (14/83), while the incidence was 11.9% for heart recipients (5/42), and 22.0% for lung recipients (9/41). Conclusions: Single-agent use with itraconazole in heart or lung transplant recipients did not affect the rate of fungal infection as compared with previous reports. The incidence of fungal infection increased significantly within 3 months after escalation of immunosuppressant for treatment of acute rejection. © Başkent University 2011.
• Park, C., Mansour, H. M., & Hayes Jr., D. (2011). Pulmonary inhalation aerosols for targeted antibiotics drug delivery. European Pharmaceutical Review.
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  Abstract: Targeted pulmonary drug delivery of antibiotics by inhalation aerosols can play significant roles in the treatment of cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and in other pulmonary diseases where chronic airway infections exist. Direct administration to the lung as targeted pulmonary inhalation aerosol delivery is uniquely able to provide for high dose levels of drugs at the target site of action without systemic side effects. This review presents an overview of pulmonary inhalation aerosols, types of inhalation aerosols, aerosol formulation additives and present current research in the targeted pulmonary drug delivery of antibiotics for the treatment of pulmonary infections. Clinical trials of antibiotic inhalation aerosols are also discussed. © Russell Publishing Limited, 2010, 2011. All rights reserved.
• Rhee, Y., & Mansour, H. M. (2011). Nanopharmaceuticals I: Nanocarrier systems in drug delivery. International Journal of Nanotechnology (Impact Factor: 1.144), 8(1-2), 84-114.
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  Abstract: To achieve maximum pharmacological effects with minimum side effects of drugs, drugs should be delivered to target sites without significant distribution to non-target areas. Using pharmaceutical nanocarrier systems for drug delivery is a useful delivery platform for improving target specificity, therapeutic activity, and reducing toxicity of drugs. Various sophisticated nanocarrier systems have been developed for drug delivery, and this review focuses on liposomes, polymeric nanoparticles, polymeric micelles, lipid nanoparticles, microemulsions, nanogels, and submicron lipid emulsions. This review outlines and explores nanocarrier systems for drug delivery by various administration routes including parenteral, oral, transdermal, pulmonary, ocular, and mucosal and discusses the product development and related issues in nanopharmaceutical drug delivery. © 2011 Inderscience Enterprises Ltd.
• Rhee, Y., Sohn, M., Woo, B. H., Thanoo, B. C., Deluca, P. P., & Mansour, H. M. (2011). Sustained-release delivery of octreotide from biodegradable polymeric microspheres. AAPS PharmSciTech (Impact Factor: 1.776), 12(4), 1293-1301.
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  PMID: 21948321;PMCID: PMC3225556;Abstract: The study reports on the drug release behavior of a potent synthetic somatostatin analogue, octreotide acetate, from biocompatible and biodegradable microspheres composed of poly-lactic-co-glycolic acid (PLGA) following a single intramuscular depot injection. The serum octreotide levels of three Oakwood Laboratories formulations and one Sandostatin LAR® formulation were compared. Three formulations of octreotide acetate-loaded PLGA microspheres were prepared by a solvent extraction and evaporation procedure using PLGA polymers with different molecular weights. The in vivo drug release study was conducted in male Sprague-Dawley rats. Blood samples were taken at predetermined time points for up to 70 days. Drug serum concentrations were quantified using a radioimmunoassay procedure consisting of radiolabeled octreotide. The three octreotide PLGA microsphere formulations and Sandostatin LAR® all showed a two-phase drug release profile (i.e., bimodal). The peak serum drug concentration of octreotide was reached in 30 min for all formulations followed by a decline after 6 h. Following this initial burst and decline, a second-release phase occurred after 3 days. This second-release phase exhibited sustained-release behavior, as the drug serum levels were discernible between days 7 and 42. Using pharmacokinetic computer simulations, it was estimated that the steady-state octreotide serum drug levels would be predicted to fall in the range of 40-130 pg/10 μL and 20-100 pg/10 μL following repeat dosing of the Oakwood formulations and Sandostatin LAR® every 28 days and every 42 days at a dose of 3 mg/rat, respectively. © 2011 American Association of Pharmaceutical Scientists.
• Xiao, W. u., & Mansour, H. M. (2011). Nanopharmaceuticals II: Application of nanoparticles and nanocarrier systems in pharmaceutics and nanomedicine. International Journal of Nanotechnology (Impact Factor: 1.144), 8(1-2), 115-145.
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  Abstract: The principle aim of using nanoparticles in pharmaceutical delivery systems is to enable targeted and efficient delivery of the appropriate levels of therapeutic or diagnostic agents to the target sites with reduced, if any, side effects to the patient. Given the benefits that nanotechnology offers, much effort has focused on producing nanoparticles for the delivery of drugs (particularly anti-tumour drugs), photosensitisers, diagnostic agents and vaccines. These nanosystems can be modified to achieve desirable biological properties (e.g., long circulation in blood, targeting delivery, stimuli sensitivity and intracellular target) and perform various therapeutically or diagnostically important functions simultaneously. This paper reviews the application of nanoparticulate systems in vaccination, chemotherapy, photodynamic therapy, diagnostics, and drug/gene delivery. Multifunctional nanocarriers are also described. Additionally, nanopharmaceutical product development and related issues are briefly presented. © 2011 Inderscience Enterprises Ltd.
• Xiao, W. u., Adedoyin, O. O., & Mansour, H. M. (2011). Pulmonary and nasal anti-inflammatory and anti-allergy inhalation aerosol delivery systems. Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry, 10(3), 215-229.
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  Abstract: Most respiratory infections, diseases and allergic reactions have varying degrees of inflammation. Inflammation is a natural immunodefensive response to the presence of allergens or foreign particles that come into contact or affect the cells and tissues within the respiratory tract. The three main types of therapeutic drug classes available for anti-inflammatory and anti-allergy effects are corticosteroids, antihistamines and decongestants. Corticosteroid drugs for pulmonary inhalation and/or nasal delivery include beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate, mometasone furoate, and triamcinolone acetonide. Antihistamine drugs for nasal delivery include azelastine and olopatadine. Two common decongestants available are oxymetazoline and phenylephrine. Another therapeutic class, the anticholinergic agents, such as ipratropium bromide and tiotropium bromide, are used in pulmonary delivery in the treatment of inflammatory diseases such as asthma and chronic obstructive pulmonary disease. The mast cell stabilizer therapeutic class, cromolyn sodium, can be used to prevent and relieve nasal allergic symptoms. Additionally cromolyn sodium was the first dry powder inhaler product for pulmonary drug delivery several decades ago and currently is on the market as a pressurized metered dose inhaler for pulmonary inhalation delivery. Based on the devices used in pulmonary drug delivery, this route can be subdivided into three categories; namely nebulizers, pressurized metered dose inhalers, and dry powder inhalers. Nasal delivery of anti-inflammatory and antiallergy drugs is most commonly available commercially in an aqueous spray form. This article comprehensively reviews and discusses different kinds of drugs used for anti-inflammatory and anti-allergic effects via the pulmonary and nasal delivery route, as well as their mechanisms of action, marketed products, disease state indications while highlighting drug delivery and therapeutic aspects. © 2011 Bentham Science Publishers Ltd.
• Xiaojian, L. i., & Mansour, H. M. (2011). Physicochemical characterization and water vapor sorption of organic solution advanced spray-dried inhalable trehalose microparticles and nanoparticles for targeted dry powder pulmonary inhalation delivery. AAPS PharmSciTech (Impact Factor: 1.776), 12(4), 1420-1430.
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  PMID: 22038473;PMCID: PMC3225514;Abstract: Novel advanced spray-dried inhalable trehalose microparticulate/ nanoparticulate powders with low water content were successfully produced by organic solution advanced spray drying from dilute solution under various spray-drying conditions. Laser diffraction was used to determine the volumetric particle size and size distribution. Particle morphology and surface morphology was imaged and examined by scanning electron microscopy. Hot-stage microscopy was used to visualize the presence/absence of birefringency before and following particle engineering design pharmaceutical processing, as well as phase transition behavior upon heating. Water content in the solid state was quantified by Karl Fisher (KF) coulometric titration. Solid-state phase transitions and degree of molecular order were examined by differential scanning calorimetry (DSC) and powder X-ray diffraction, respectively. Scanning electron microscopy showed a correlation between particle morphology, surface morphology, and spray drying pump rate. All advanced spray-dried microparticulate/nanoparticulate trehalose powders were in the respirable size range and exhibited a unimodal distribution. All spray-dried powders had very low water content, as quantified by KF. The absence of crystallinity in spray-dried particles was reflected in the powder X-ray diffractograms and confirmed by thermal analysis. DSC thermal analysis indicated that the novel advanced spray-dried inhalable trehalose microparticles and nanoparticles exhibited a clear glass transition (T g). This is consistent with the formation of the amorphous glassy state. Spray-dried amorphous glassy trehalose inhalable microparticles and nanoparticles exhibited vapor-induced (lyotropic) phase transitions with varying levels of relative humidity as measured by gravimetric vapor sorption at 25°C and 37°C. © 2011 American Association of Pharmaceutical Scientists.
• Zhen, X. u., Mansour, H. M., & Hickey, A. J. (2011). Particle interactions in dry powder inhaler unit processes: A review. Journal of Adhesion Science and Technology (Impact Factor: 1.175), 25(4-5), 451-482.
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  Abstract: Recent development and methods of designing and optimizing dry powder formulations have extended the therapeutic potential of inhaled dosage forms. Successful drug delivery as indicated by a high and reproducible fine particle fraction, required to achieve the desired therapeutic effect while minimizing potential toxicity, depends on an understanding of the physico-chemical properties of powder blends, their performance and availability of adequate tools to screen and predict their behavior. The scope of this review includes three important perspectives for inhaled drug delivery: (1) Fundamental aspects of interparticulate interactions of pharmaceutical dry powder aerosols at rest and in resuspension; (2) The influences of pharmaceutical processing including milling, mixing, filling and storage, and their influence on powder dispersion; (3) Current strategies for formulation optimization and methods for in vitro aerosolization performance prediction. © 2011 VSP.
• Hayes Jr., D., Zwischenberger, J. B., & Mansour, H. M. (2010). Aerosolized tacrolimus: A case report in a lung transplant recipient. Transplantation Proceedings (Impact Factor: 1.061), 42(9), 3876-3879.
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  PMID: 21094875;Abstract: Long-term outcomes after lung transplantation remain poor mainly to the development of bronchiolitis obliterans syndrome (BOS). Currently, treatment options for BOS are very limited. Strategies to prevent and treat this complication include the use of aerosolized therapy with only cyclosporine used in patients to date. We describe the use of aerosolized tacrolimus in a lung transplant recipient with BOS. The patient demonstrated clinical improvement in functional capacity and oxygenation while receiving tacrolimus by nebulization. Further research is needed to study whether aerosolized tacrolimus is beneficial in lung transplant recipients with BOS. © 2010 by Elsevier Inc. All rights reserved.
• Mansour, H. M., Sohn, M., Al-Ghananeem, A., & DeLuca, P. P. (2010). Materials for pharmaceutical dosage forms: Molecular pharmaceutics and controlled release drug delivery aspects. International Journal of Molecular Sciences (Impact Factor: 2.339), 11(9), 3298-3322.
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  PMID: 20957095;PMCID: PMC2956096;Abstract: Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development. © 2010 by the authors; licensee MDPI, Basel, Switzerland.
• Mansour, H. M., Zhen, X. u., & Hickey, A. J. (2010). Dry powder aerosols generated by standardized entrainment tubes from alternative sugar blends: 3. Trehalose dihydrate and D-mannitol carriers. Journal of Pharmaceutical Sciences (Impact Factor: 3.007), 99(8), 3430-3441.
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  PMID: 20229601;Abstract: The relationship between physicochemical properties of drug/carrier blends and aerosol drug powder delivery was evaluated. Four pulmonary drugs each representing the major pulmonary therapeutic classes and with a different pharmacological action were employed. Specifically, the four pulmonary drugs were albuterol sulfate, ipratropium bromide monohydrate, disodium cromoglycate, and fluticasone propionate. The two carrier sugars, each representing a different sugar class, were D-mannitol and trehalose dihydrate. Dry powder aerosols (2%, w/w, drug in carrier) delivered using standardized entrainment tubes (SETs) were characterized by twin-stage liquid impinger. The fine particle fraction (FPF) was correlated with SET shear stress, τs, and the maximum fine particle fraction (FPFmax) was correlated with a deaggregation constant, kd, by using a powder aerosol deaggregation equation (PADE) by nonlinear and linear regression analyses applied to pharmaceutical inhalation aerosol systems in the solid state. For the four pulmonary drugs representing the major pulmonary therapeutic classes and two chemically distinct pulmonary sugar carriers (non-lactose types) aerosolized with SETs having well-defined shear stress values, excellent correlation and predictive relationships were demonstrated for the novel and rigorous application of PADE for dry powder inhalation aerosol dispersion within a well-defined shear stress range, in the context of pulmonary drug/sugar carrier physicochemical and interfacial properties. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association.
• Xiao, W. u., Xiaojian, L. i., & Mansour, H. M. (2010). Surface analytical techniques in solid-state particle characterization for predicting performance in dry powder inhalers. KONA Powder and Particle Journal (Impact Factor: 1.227), 28, 3-19.
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  Abstract: The pulmonary route is of interest for both ef fective local therapy for respiratory and lung diseases, such as asthma, chronic obstructive pulmonary disease and cystic fibrosis, and systemic administration of drugs, such as proteins and peptides. Dry powder inhalers (DPIs) are devices through which a dry powder formulation of drug is delivered via the pulmonary route. The DPIs are highly efficient but complicated systems, the performance of which relies on many aspects, including aerodynamic diameter of the powder formulation, particle density, bulk density, surface morphology and composition, particle shape, interparticulate cohesive forces between drug particles and interparticulate adhesive forces between drug and carrier particles. Among them, surface morphology of both drug particles and carrier particles within the formulation is a very important factor in determining the interparticulate contact area and forces, aerosolization efficiency and subsequent lung deposition. Techniques that have been applied to study surface properties of solidstate particles in DPIs include atomic force microscopy, micro-and nanothermal analysis, inverse gas chromatography and X-ray photoelectron spectroscopy. This paper reviews different aspects of DPIs, with emphasis on their surface properties and influence on aerosol performance, and the techniques that are utilized to examine their surface properties. © 2010 Hosokawa Powder Technology Foundation.
• Zhen, X. u., Mansour, H. M., Mulder, T., McLean, R., Langridge, J., & Hickey, A. J. (2010). Heterogeneous particle deaggregation and its implication for therapeutic aerosol performance. Journal of Pharmaceutical Sciences (Impact Factor: 3.007), 99(8), 3442-3461.
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  PMID: 20232454;Abstract: Aerosolization performance of dry powder blends of drugs for the treatment of asthma or chronic obstructive pulmonary diseases have been reported in three previous articles. In vitro aerosolization was performed at defined shear stresses (0.624-13.143 N/m2). Formulations were characterized aerodynamically and powder aerosol deaggregation equations (PADE) and corresponding linear regression analyses for pharmaceutical aerosolization were applied. Particle deaggregation is the result of overcoming fundamental forces acting at the particle interface. A new method, PADE, describing dry powder formulation performance in a shear stress range has been developed which may allow a fundamental understanding of interparticulate and surface forces. The application of PADE predicts performance efficiency and reproducibility and supports rational design of dry powder formulations. The analogy of aerosol performance with surface molecular adsorption has important implications. Expressions describing surface adsorption were intended to allow elucidation of mechanisms involving surface heterogeneity, lateral interaction, and multilayer adsorption of a variety of materials. By using a similar expression for drug aerosolization performance, it is conceivable that an analogous mechanistic approach to the evaluation of particulate systems would be possible. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association.
• Zhen, X. u., Mansour, H. M., Mulder, T., Mclean, R., Langridge, J., & Hickey, A. J. (2010). Dry powder aerosols generated by standardized entrainment tubes from drug blends with lactose monohydrate: 1. Albuterol sulfate and disodium cromoglycate. Journal of Pharmaceutical Sciences (Impact Factor: 3.007), 99(8), 3398-3414.
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  PMID: 20198688;Abstract: The major objective of this study was: discriminatory assessment of dry powder aerosol performance using standardized entrainment tubes (SETs) and lactose-based formulations with two model drugs. Drug/lactose interactive physical mixtures (2%w/w) were prepared. Their properties were measured: solid-state characterization of phase behavior and molecular interactions by differential scanning calorimetry and X-ray powder diffraction; particle morphology and size by scanning electron microscopy and laser diffraction; aerosol generation by SETs and characterization by twin-stage liquid impinger and Andersen cascade impactor operated at 60 L/min. The fine particle fraction (FPF) was correlated with SET shear stress (τs), using a novel powder aerosol deaggregation equation (PADE). Drug particles were
• Zhen, X. u., Mansour, H. M., Mulder, T., Mclean, R., Langridge, J., & Hickey, A. J. (2010). Dry powder aerosols generated by standardized entrainment tubes from drug blends with lactose monohydrate: 2. Ipratropium bromide monohydrate and fluticasone propionate. Journal of Pharmaceutical Sciences (Impact Factor: 3.007), 99(8), 3415-3429.
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  PMID: 20222025;Abstract: The objectives of this study were: systematic investigation of dry powder aerosol performance using standardized entrainment tubes (SETs) and lactose-based formulations with two model drugs; mechanistic evaluation of performance data by powder aerosol deaggregation equation (PADE). The drugs (IPB and FP) were prepared in sieved and milled lactose carriers (2% w/w). Aerosol studies were performed using SETs (shear stresses τs=0.624-13. 143N/m2) by twin-stage liquid impinger, operated at 60 L/min. PADE was applied for formulation screening. Excellent correlation was observed when PADE was adopted correlating FPF to τs. Higher τs corresponded to higher FPF values followed by a plateau representing invariance of FPF with increasing τs. The R2 values for PADE linear regression were 0.9905-0.9999. Performance described in terms of the maximum FPF (FPFmax: 15.0-37.6%) resulted in a rank order of ML-B/IPB>ML-A/IPB>SV-A/IPB>SV-B/IPB>ML-B/FP>ML-A/FP>SV-B/ FP>SV-A/FP. The performance of IPB was superior to FP in all formulations. The difference in lactose monohydrate carriers was less pronounced for the FPF in IPB than in FP formulations. The novel PADE offers a robust method for evaluating aerodynamic performance of dry powder formulations within a defined τs range. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association.
• Mansour, H. M., Rhee, Y., & Xiao, W. u. (2009). Nanomedicine in pulmonary delivery.. International journal of nanomedicine (Impact Factor: 4.195), 4, 299-319.
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  PMID: 20054434;PMCID: PMC2802043;Abstract: The lung is an attractive target for drug delivery due to noninvasive administration via inhalation aerosols, avoidance of first-pass metabolism, direct delivery to the site of action for the treatment of respiratory diseases, and the availability of a huge surface area for local drug action and systemic absorption of drug. Colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery offer many advantages such as the potential to achieve relatively uniform distribution of drug dose among the alveoli, achievement of improved solubility of the drug from its own aqueous solubility, a sustained drug release which consequently reduces dosing frequency, improves patient compliance, decreases incidence of side effects, and the potential of drug internalization by cells. This review focuses on the current status and explores the potential of colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with special attention to their pharmaceutical aspects. Manufacturing processes, in vitro/in vivo evaluation methods, and regulatory/toxicity issues of nanomedicines in pulmonary delivery are also discussed.
• Mansour, H. M., Damodaran, S., & Zografi, G. (2008). Characterization of the in situ structural and interfacial properties of the cationic hydrophobic heteropolypeptide, KL₄, in lung surfactant bilayer and monolayer models at the air - Water interface: Implications for pulmonary surfactant delivery. Molecular Pharmaceutics (Impact Factor: 4.787), 5(5), 681-695.
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  PMID: 18630875;Abstract: This study examines the various equilibrium in situ secondary structures of the pharmaceutical heteropolypeptide, KL4, in the solid state, in solution, and in the monolayer state alone and mixed with dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylglycerol (POPG). In situ surface circular dichroism spectroscopy, using a method first reported by Damodaran (Damodaran, S. Anal. Bioanal. Chem. 2003, 376, 182-188), of equilibrated KL4, DPPC/KL4, POPG/KL4, and DPPC/POPG/KL4 monolayers at the air - water interface was used to examine the in situ two-dimensional conformation of KL4. Gravimetric vapor sorption by solid KL4 was used to analyze the effects of water molecules on the conformation of KL4 when confined as a monolayer at the surface of water. Solid-state KL4 conformation was determined by X-ray powder diffraction (XRPD). The equilibrium interfacial and spreading properties were measured at 25 °C, 37 °C, and 45 °C using the Wilhelmy plate method and Langmuir film balance. Equilibrium phase transition temperatures were measured using differential scanning calorimetry (DSC). It was found that solid-state KL4, which takes up very little water, exhibits β-sheet and α-helix secondary structures, whereas KL4 in solution appears to exist only as an α-helix. KL4 forms a stable, insoluble monolayer, exhibiting β-sheet and aperiodic structures. These structures provide KL4, when confined in two-dimensions, the structural flexibility to maximize favorable cationic lysine-water interactions and favorable leucine - leucine hydrophobic and van der Waals interactions; while effectively "shielding" the leucine residues away from water. In DPPC/KL4 monolayers, KL4 retains its native β-sheet and aperiodic structures, consistent with phase separation of DPPC and KL4, in bilayers and monolayers. In POPG/KL4 monolayers, KL4 exhibits an increase in aperiodic secondary structures (loss of β-sheet) to maximize favorable electrostatic interactions, consistent with the observed negative deviations from ideal monolayer mixing. © 2008 American Chemical Society.
• Hickey, A. J., Mansour, H. M., Telko, M. J., Zhen, X. u., Smyth, H. D., Mulder, T., Mclean, R., Langridge, J., & Papadopoulos, D. (2007). Physical characterization of component particles included in dry powder inhalers. I. Strategy review and static characteristics. Journal of Pharmaceutical Sciences (Impact Factor: 3.007), 96(5), 1282-1301.
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  PMID: 17455324;Abstract: The performance of dry powder aerosols for the delivery of drugs to the lungs has been studied extensively in the last decade. The focus for different research groups has been on aspects of the powder formulation, which relate to solid state, surface and interfacial chemistry, bulk properties (static and dynamic) and measures of performance. The nature of studies in this field, tend to be complex and correlations between specific properties and performance seem to be rare. Consequently, the adoption of formulation approaches that on a predictive basis lead to desirable performance has been an elusive goal but one that many agree is worth striving towards. The purpose of this paper is to initiate a discussion of the use of a variety of techniques to elucidate dry particle behavior that might guide the data collection process. If the many researchers in this field can agree on this, or an alternative, guide then a database can be constructed that would allow predictive models to be developed. This is the first of two papers that discuss static and dynamic methods of characterizing dry powder inhaler formulations. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association.
• Hickey, A. J., Mansour, H. M., Telko, M. J., Zhen, X. u., Smyth, H. D., Mulder, T., Mclean, R., Langridge, J., & Papadopoulos, D. (2007). Physical characterization of component particles included in dry powder inhalers. II. Dynamic characteristics. Journal of Pharmaceutical Sciences (Impact Factor: 3.007), 96(5), 1302-1319.
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  PMID: 17455364;Abstract: Characteristics of particles included in dry powder inhalers is extended from our previous report (in this journal) to include properties related to their dynamic performance. The performance of dry powder aerosols for pulmonary delivery is known to depend on fluidization and dispersion which reflects particle interactions in static powder beds. Since the solid state, surface/interfacial chemistry and static bulk properties were assessed previously, it remains to describe dynamic performance with a view to interpreting the integrated database. These studies result in complex data matrices from which correlations between specific properties and performance may be deduced. Lactose particles were characterized in terms of their dynamic flow, powder and aerosol electrostatics, and aerodynamic performance with respect to albuterol aerosol dispersion. There were clear correlations between flow properties and aerosol dispersion that would allow selection of lactose particles for formulation. Moreover, these properties can be related to data reported earlier on the morphological and surface properties of the carrier lactose particles. The proposed series of analytical approaches to the evaluation of powders for inclusion in aerosol products has merit and may be the basis for screening and ultimately predicting particle performance with a view to formulation optimization. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association.
• Mansour, H. M., & Hickey, A. J. (2007). Raman characterization and chemical imaging of biocolloidal self-assemblies, drug delivery systems, and pulmonary inhalation aerosols: A review. AAPS PharmSciTech (Impact Factor: 1.776), 8(4).
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  PMID: 18181559;PMCID: PMC2750560;Abstract: This review presents an introduction to Raman scattering and describes the various Raman spectroscopy, Raman microscopy, and chemical imaging techniques that have demonstrated utility in biocolloidal self-assemblies, pharmaceutical drug delivery systems, and pulmonary research applications. Recent Raman applications to pharmaceutical aerosols in the context of pulmonary inhalation aerosol delivery are discussed. The "molecular fingerprint" insight that Raman applications provide includes molecular structure, drug-carrier/excipient interactions, intramolecular and intermolecular bonding, surface structure, surface and interfacial interactions, and the functional groups involved therein. The molecular, surface, and interfacial properties that Raman characterization can provide are particularly important in respirable pharmaceutical powders, as these particles possess a higher surface-area-to-volume ratio; hence, understanding the nature of these solid surfaces can enable their manipulation and tailoring for functionality at the nanometer level for targeted pulmonary delivery and deposition. Moreover, Raman mapping of aerosols at the micro- and nanometer level of resolution is achievable with new, sophisticated, commercially available Raman microspectroscopy techniques. This noninvasive, highly versatile analytical and imaging technique exhibits vast potential for in vitro and in vivo molecular investigations of pulmonary aerosol delivery, lung deposition, and pulmonary cellular drug uptake and disposition in unfixed living pulmonary cells.
• Mansour, H. M., & Zografi, G. (2007). Relationships between equilibrium spreading pressure and phase equilibria of phospholipid bilayers and monolayers at the air-water interface. Langmuir (Impact Factor: 4.384), 23(7), 3809-3819.
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  PMID: 17323986;Abstract: The intricate interplay between the bilayer and monolayer properties of phosphatidylcholine (PC), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) phospholipids, in relation to their polar headgroup properties, and the effects of chain permutations on those polar headgroup properties have been demonstrated for the first time with a set of time-independent bilayer-monolayer equilibria studies. Bilayer and monolayer phase behavior for PE is quite different than that observed for PC and PG. This difference is attributed to the characteristic biophysical PE polar headgroup property of favorable intermolecular hydrogen-bonding and electrostatic interactions in both the bilayer and monolayer states, This characteristic hydrogen-bonding ability of the PE polar headgroup is reflected in the condensed nature of PE monolayers and a decrease in equilibrium monolayer collapse pressure at temperatures below the monolayer critical temperature, Tc (whether above or below the monolayer triple point temperature, Tc. This interesting phenomena is compared to equilibrated PC and PG monolayers which collapse to form bilayers at 45 mN/m at temperatures both above and below monolayer Tc. Additionally, it has been demonstrated by measurements of the equilibrium spreading pressure, πe, that at temperatures above the bilayer main gel-to-liquid-crystalline phase-transition temperature, Tm, all liquid-crystalline phospholipid bilayers spread to form monolayers with πe, around 45 mN/m, and spread liquid-expanded equilibrated monolayers collapse at 45 mN/m to form their respective thermodynamically stable liquidcrystalline bilayers. At temperatures below bilayer Tm, PC and PG gel bilayers exhibit a drop in bilayer πe values ≤0.2 mN/m forming gaseous monolayers, whereas the value of ≤c of spread monolayers remains around 45 mN/m. This suggests that spread equilibrated PC and PG monolayers collapse to a metastable liquid-crystalline bilayer structure at temperatures below bilayer Tm (where the thermodynamically stable bilayer liquid-crystalline phase does not exist) and with a surface pressure of 45 mN/m, a surface chemical property characteristically observed at temperatures above bilayer Tm (monolayer Tc). In contrast, PE gel bilayers, which exist at temperatures below bilayer Tm but above bilayer Ts, (bilayer crystal-to-gel phase-transition temperature), exhibit gel bilayer spreading to form equilibrated monolayers with intermediate ≤e, values in the range of 30-40 mN/m; however, bilayer ne and monolayer ≤c values remain equal in value to one another. Contrastingly, at temperatures below bilayer Ts, PE crystalline bilayers exhibit bilayer ≤e, values ≤0.2 mN/m forming equilibrated gaseous monolayers, whereas spread monolayers collapse at a value of ≤c remaining around 30 mN/m, indicative of metastable gel bilayer formation. © 2007 American Chemical Society.
• Mansour, H. M., & Zografi, G. (2007). The relationship between water vapor absorption and desorption by phospholipids and bilayer phase transitions. Journal of Pharmaceutical Sciences (Impact Factor: 3.007), 96(2), 377-396.
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  PMID: 17080427;Abstract: Water vapor absorption and desorption at 25°C and phase transition temperatures of phospholipid bilayers were measured as a function of relative humidity (RH) to better understand how the patterns of water vapor absorption and desorption are linked to corresponding phase changes induced by the level of hydration. Comparisons were made of the dipalmitoyl and palmitoyloleyol esters of glycerol derivatized with phosphatidyl-choline, -glycerol, -ethanolamine and with phosphatidic acid. The results suggest that the extent of water vapor absorption and desorption at a given RH reflects the combined effects of water-polar group interaction and access of water to the polar region as controlled by intra- and interbilayer molecular packing and intermolecular attractive and repulsive interactions. The results further suggest that the extent of water vapor absorption and desorption over a range of relative humidities reflects the combined effects of the polar group's ability to interact with water, the access that water has to the polar groups as determined by molecular size and various intermolecular and intrabilayer forces of attraction and repulsion, and interbilayer interactions which influence the degree of order/disorder present in the overall solid-state structure. This behavior is also reflected in the changes observed in the various bilayer phase transition temperatures as a function of RH. Analyses of absorption isotherms suggests that after exceeding a critical RH, water initially interacting with these phospholipids most likely forms either stoichiometric or nonstoichiometric crystal hydrates, as with the disaturated derivatives, or hydrated mesophases, as with the gel states of the monounsaturated derivatives. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association.
• Mansour, H., Wang, D., Chen, C., & Zografi, G. (2001). Comparison of bilayer and monolayer properties of phospholipid systems containing dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylinositol. Langmuir (Impact Factor: 4.384), 17(21), 6622-6632.
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  Abstract: Bilayer and monolayer phase behavior at the air-water interface of dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidylinositol (DPPI), and their binary mixtures with dipalmitoylphosphatidylcholine (DPPC), in the context of their possible roles in lung surfactant function, have been systematically compared. Surface properties, as a function of temperature and composition, were evaluated and analyzed by measuring equilibrium surface pressure-area isotherms (π-A), equilibrium monolayer collapse pressure (πc), and minimum area per molecule at the monolayer collapse pressure (Ac) and by direct observation using fluorescence microscopy. Bilayer properties were evaluated by measuring the main bilayer phase transition temperature (Tm) and the bilayer equilibrium spreading pressure (πe) as a function of temperature and composition. Through thermodynamic analysis, it was found that DPPC/DPPG mix ideally in both the monolayer and bilayer states, whereas DPPC/DPPI (further supported with DPPC/Soy PI) are phase-separated with partial miscibility in bilayers and miscible with very significant positive deviations from ideality in monolayers. This behavior is attributed to the distinct differences between PG and PI headgroup properties as reflected in their physical size, state of hydration, and possible conformational flexibility, despite identical net negative charge and identical acyl chain headgroup properties. PC and PG exhibit very similar headgroup properties, which allow the dipalmitoyl chain properties to dominate over headgroup effects in bilayers and monolayers. In contrast, the unique PI headgroup properties dominate over the dipalmitoyl chain effects giving rise to very different surface and bilayer phase behavior.

Proceedings Publications

• Sears, S., Acosta, M. F., Tang, H., Klinger, C., Yuan, J. X., Mansour, H., & Black, S. M. (2018, May/Spring). Inhaled L-Carnitine Attenuates the Development of Pulmonary Arterial Hypertension in Rats. In Am J Respir Crit Care Med. The American Thoracic Society (ATS) Conference & Exhibition. B59. SHOOT THE CURL: SPLASHING INTO MECHANISMS OF ENDOTHELIAL CELL FUNCTION AND VASCULAR REMODELING IN PH (Thematic Poster Session)., 197, A3743.
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  American Journal of Respiratory and Critical Care Medicine 2018;197:A3743B59. SHOOT THE CURL: SPLASHING INTO MECHANISMS OF ENDOTHELIAL. Thematic Poster Session.
• Acosta, M. F., Hayes, D., Fineman, J. R., Black, S. M., & Mansour, H. M. (2017, June). IMPROVEMENT OF THE IN VITRO AEROSOL DISPERSION PERFORMANCE OF SIMVASTATIN BY CO-SPRAY DRYING WITH D-MANNITOL FOR THE TREATMENT OF PULMONARY HYPERTENSION. Poster Presentation & Published Journal Abstract.. In 2017 ISAM Congress, 30, 12.
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  JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY-abstract journal pubposter presentation at 2017 ISAM Congress
• Hecker, L., Gokhale, V., Knox, K. S., Mansour, H. M., & Garcia, J. G. (2017, May). Identification Of Selective And Effective Small-Molecule Inhibitors Targeting Nox4. Poster Presentation & Published Journal Abstract.. In Am J Respir Crit Care Med. The American Thoracic Society (ATS) International Annual Conference & Exhibition. C78. FIBROSIS: MEDIATORS AND MODULATORS., 195, A6421.
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  ATS International Annual Conference & ExhibitionSession C78. FIBROSIS: MEDIATORS AND MODULATORSAm J Respir Crit Care Med 2017;195:A6421
• Mallory, E. K., Malapit, M., Muralidharan, P., Phan, H., Hayes, D., & Mansour, H. M. (2017, May). In Vitro Aerodynamic Analysis Of Co-Spray Dried Fluticasone Propionate (fp) And Salmeterol Xinafoate (sx) Dry Powder Inhalation. Poster Presentation & Published Journal Abstract. Aerosols With Lactose-Alternative Excipient. In Am J Respir Crit Care Med. The American Thoracic Society (ATS) International Annual Conference & Exhibition. C73 NEW MECHANISMS AND THERAPIES IN COPD / Thematic Poster Session., 195, A6271.
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  invited poster presentation authored by my graduate students, PharmD students, PhPr faculty colleague, COM colleague, and myself.C73 NEW MECHANISMS AND THERAPIES IN COPD / Thematic Poster Session.Am J Respir Crit Care Med 2017;195:A6271
• Muralidharan, P., Hayes, D., Yuan, J. X., Black, S. M., & Mansour, H. M. (2017, June). COMPARISON OF IN VITRO AEROSOL DISPERSION PERFORMANCE USING DIFFERENT DRY POWDER INHALER DEVICES. Poster Presentation & Journal Published Abstract.. In 2017 ISAM Congress, 30, 33.
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  JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY-abstract journal pubposter presentation at 2017 ISAM Congress
• Hayes, Jr, D., Tobias, J. D., Mansour, H. M., Kirkby, S., McCoy, K. S., Galantowicz, M., & Whitson, B. A. (2014, October). Pulmonary Hypertension in Cystic Fibrosis in Relation to Other Lung Diseases Prior to Lung Transplantation.. In Pediatric Pulmonology Journal (Impact Factor: 2.297): 2014 North American Cystic Fibrosis Conference (NACFC) Annual Meeting, 49, 374-375.
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  Pediatric Pulmonology Journal (2014) 49 (S38): 374-375. (Impact Factor: 2.297)(poster presentation 437 at the 2014 North American Cystic Fibrosis Conference (NACFC) Annual Meeting, Atlanta, GA. (October 2014)
• Mansour, H. M. (2014, October). Influence of Diabetes on Survival in Cystic Fibrosis Before and After Lung Transplantation.. In Pediatric Pulmonology Journal (Impact Factor: 2.297): 2014 North American Cystic Fibrosis Conference (NACFC) Annual Meeting, 49, 425.
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  (poster presentation 567 at the 2014 North American Cystic Fibrosis Conference (NACFC) Annual Meeting, Atlanta, GA. (October 2014)(2014) 49 (S38): 425. (Impact Factor: 2.297)

Presentations

• Mansour, H. M. (2020, August/Summer). Webinar Presentation Title: “Building a Strong Research Career”. NIH BUILD (Building Infrastructure Leading to Diversity) and the Diversity Program Consortium Summer Webinar Series. Texas: NIH BUILD (Building Infrastructure Leading to Diversity) and the Diversity Program Consortium.
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  invited NIH webinar hosted by the Univ of Texas- El PasoNIH BUILD Scholars & the Diversity Program Consortium, Univ of Texas-El Paso 08/20--NIH BUILD Scholars Summer Seminar Series Invited Speaker-Webinar Presentation Title: “Building a Strong Research Career”
• Mansour, H. (2019, May/Spring). Invited Expert Panelist: Where are the Opportunities, Challenges in Airway Disease. Respiratory Innovation Summit (RIS), Dallas, TX. Dallas, Tx.
• Mansour, H. M. (2019, Feb 2019). Invited Seminar Presentation: Nanotechnology. Meijo Univ. (Japan) Visiting Delegation. Tucson: Meijo Univ & The UA COP.
• Mansour, H. (2018, April/Spring). Drug Delivery Research in the new BS PharmSci program. UA Admitted Students' Day/UA Spring Fling. UA Integrated Learning Center, Tucson, AZ: The UA COP BSPS Program.
• Mansour, H. (2018, April/Spring). Invited Faculty Guest Panelist: Tips on Mentoring Student Research. UA COP Fellowship Program. UA COP, Tucson, AZ: UA COP Fellowship Program.
• Mansour, H. (2018, April/Spring). Invited Faculty Speaker on Mentoring Women in STEM. Latin-American Program, UA Global Initiatives, The UA Office of Diversity & Inclusion. Tucson, AZ: UA Global Initiatives in The UA Office of Diversity & Inclusivity.
• Mansour, H. (2018, November 2018). Nanotechnology and Drug Regulation. Regulatory Science Seminar Series. Tucson, AZ: UAHS & College of Law.
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  Regulatory Science Seminar Series, Invited Seminar Speaker, Seminar Title: "Nanotechnology and Drug Regulation", Nov. 13, 2018, UAHS & UA College of Law (Tucson, AZ).
• Mansour, H. (2018, October 2018). Advances and Innovation in Inhalation Aerosols. The UAHS Asthma & Airway Disease Research Center (A2DRC) Seminar Series. Tucson, AZ: The UAHS Asthma & Airway Disease Research Center (A2DRC).
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  A2DRC Invited Seminar Speaker, Seminar Title: "Advances and Innovation in Inhalation Aerosols", Oct. 25, 2018 (Tucson, AZ).
• Mansour, H. M. (2018, October). Faculty Instructor Presentation "Challenges and Opportunities of 'Nano' in Pulmonary Administration”. Aerosol School-International Society of Aerosols in Medicine (ISAM). Firestone Institute for Respiratory Health, McMaster Univ. & St. Joseph's Healthcare, Hamilton, Ontario, Canada: International Society of Aerosols in Medicine (ISAM).
• Mansour, H. (2017, March 2017). Invited Speaker. 10th International Conference Neonatal & Childhood Pulmonary Vascular Disease. San Francisco, CA: UCSF COM.
• Mansour, H. M. (2017, Fall 2107). Invited Seminar Presentation: Nanotechnology. Meijo Univ. (Japan) Visiting Delegation. Tucson: Meijo Univ & The UA COP.
• Mansour, H. M. (2017, October 2017). Dean's Invited Speaker. The National Advisory Board (NAB) visit to The UA COP. Tucson, AZ: NAB & The UA COP Dean's Administration.
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  Dean's Invited Speaker to present my research to the NAB during their onsite visit to The UA COP
• Mansour, H. M. (2017, October). Faculty Instructor Presentation "Challenges and Opportunities of 'Nano' in Pulmonary Administration”. Aerosol School-International Society of Aerosols in Medicine (ISAM). Firestone Institute for Respiratory Health, McMaster Univ. & St. Joseph's Healthcare, Hamilton, Ontario, Canada: International Society of Aerosols in Medicine (ISAM).
• Mansour, H. M. (2017, Sept/Fall 2017). Invited Seminar Presentation: My Background and Research Program as a Pharmacist and Faculty Researcher.. UA Pre-Pharmacy Club. Tucson, AZ: UA Pre-Pharmacy Club.
• Grijalva, C. L., Pina, A., Acosta, M. F., Gomez, A. I., Muralidharan, P., Hayes Jr, D., Black, S. M., & Mansour, H. M. (2016, November). Comparison of the In Vitro Aerosol Dispersion Performance of a Nrf2 Activator Using Two Different Human Dry Powder Inhaler Devices.. Society of Hispanic Professional Engineers (SHPE) Conference. Seattle, WA: SHPE.
• Grijalva, C. L., Pina, A., Acosta, M. F., Gomez, A. I., Muralidharan, P., Hayes Jr, D., Black, S. M., & Mansour, H. M. (2016, October). Comparison of the In Vitro Aerosol Dispersion Performance of a Nrf2 Activator Using Two Different Human Dry Powder Inhaler Devices.. 17th National Role Models Conference. Washington, D.C.: The NSF (National Science Foundation).
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  oral presentation-3rd Place Best Student Research Oral Presentation Award
• Hayes Jr, D., Tumin, D., Kirikby, S., Mansour, H. M., Tobias, J. D., & Kopp, B. T. (2016, October). Transplant Center Cystic Fibrosis-Specific Expertise and Outcome of Lung Transplantation.. 2016 North American Cystic Fibrosis Conference (NACFC) Annual Meeting. Orlando, FL: North American Cystic Fibrosis Society.
• Mansour, H. (2016, February). Translational & Regenerative Pulmonary Medicine Research Invited Speaker. Skip Garcia's Invited Faculty Speaker at Garcia Group Meeting. Tucson, AZ: UA College of Medicine, Dept of Medicine.
• Mansour, H. M. (2016, April). Nanotechnology Research. UA COP Osaka University (Japan) Visiting Pharmacy Students, Graduate Students, and Faculty Member. Tucson, AZ: UA COP Osaka University.
• Mansour, H. M. (2016, December). Particle Design, Nanotechnology, and Advanced Drug Delivery for Translational Medicine.. Invited Seminar Series at the UA College of Engineering, Chemical and Environmental Engineering Dept. Tucson, AZ: UA College of Engineering, Chemical and Environmental Engineering Dept.
• Mansour, H. M. (2016, July). Co-Chair-Scientific Symposium "New Processes, New Materials, and New Products.". Controlled Release Society (CRS). Seattle, WA: Controlled Release Society (CRS).
• Mansour, H. M. (2016, June). Advances in Biomimetic Nanomaterials for Multifunctional Inhalation Aerosols in Pulmonary Biomedicine. American Chemical Society (ACS) 90th Colloid & Surface Science Symposium on Nanomaterials for Biomedicine. Harvard Univ. Cambridge, MA.: American Chemical Society (ACS) Division Colloid & Surface Science.
• Mansour, H. M. (2016, May). dr-heidi-mansour-develops-inhalers-treat-lung-diseases. UA College of Medicine, Dept of Medicine, faculty research news plus HMM Research Lab Presentation videoUA College of Medicine, Dept of Medicine, faculty research news plus video.
• Mansour, H. M. (2016, October). Faculty Instructor Presentation "Challenges and Opportunities of 'Nano' in Pulmonary Administration”. Aerosol School-International Society of Aerosols in Medicine (ISAM). Hamilton, Ontario, Canada: International Society of Aerosols in Medicine (ISAM).
• Mansour, H. M., & Brain, J. (2016, Janaury). nvited Webinar Presentation Title: “Pharmacology of Inhaled Therapeutics”. Invited Webinar “Mechanisms & Pharmacology of Inhaled Drug Delivery”. Online: Aerogen.
• Gomez, A., Acostaa, M., & Mansour, H. M. (2015, summer). Advanced Spray Dried Proliposomes as Dry Powder Inhaler: An Advanced Drug Delivery System for Pulmonary Administration. Alexan Gomez & Maria Acosta (Research Fellow Student Presenters). NSF UA UROC Research Conference,. Tucson, AZ: NSF UA UROC.
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  Gomez, A. I., Acosta, M.F., and Mansour, H.M. Advanced Spray Dried Proliposomes as Dry Powder Inhaler: An Advanced Drug Delivery System for Pulmonary Administration. NSF UA UROC Research Conference, Tucson, AZ. (August 2015).
• Mansour, H. (2015, Spring). Nanotechnology in Pharmacy. Meijo University (Japan) Visiting Pharmacy Students, Graduate Students, and Faculty Members. Tucson, AZ: Dr. Mike Katz International Program.
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  Meijo University (Japan) Visiting Pharmacy Students, Graduate Students, and Faculty Members 2015 -Presentation Title: "Nanotechnology in Pharmacy"
• Mansour, H. (2015, summer). Inhalation Pharmaceuticals: Device Design and Formulations. Inhalation Magazine Invited Webinar Annual Speaker.. Webinar-a record high number of 300 webinar registrants: Inhalation Magazine.
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  Inhalation Magazine Invited Webinar Annual Speaker 2015 -Title: “Inhalation Pharmaceuticals: Device Design and Formulations” -a record high number of 300 webinar registrants [link]
• Mansour, H. M. (2015, December). Faculty “Who We Are” Spotlight Speaker. UA COP Faculty Retreat, Westin LaPaloma Resort. Tucson, AZ: UA COP.
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  UA COP Faculty Retreat, Westin LaPaloma Resort 2015 -Faculty “Who We Are” Spotlight Speaker
• Mansour, H. M. (2015, Spring). Influence of Transfusion on Survival in Lung Transplantation. American Thoracic Society (ATS) International Conference,. Denver, CO.: The American Thoracic Society (ATS).
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  Hayes, D. Jr, Whitson, B.A., Black, S.M., Mansour, H.M., Tobias, J.D., Nicol, K.K., Yates, A.R., Preston, T.J., and Palmer, A.F. Influence of Transfusion on Survival in Lung Transplantation. 2015 American Thoracic Society (ATS) International Conference, Denver, CO. (May 2015). American Journal of Respiratory & Critical Care Medicine (2015) 191: A2237. (Impact Factor: 12.996)
• Mansour, H. M. (2015, Spring). Invited Symposium Speaker Presentation: "Advances in Targeted Multifunctional Inhalation Aerosols with Nanotechnology and Solid-State Particle Engineering Design”. American Chemical Society (ACS) 249th Annual Meeting & Exhibition. Division of Colloid & Surface Chemistry.Symposium: “Advances in Formulations Science & Technology”. Denver, CO.: ACS.
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  American Chemical Society (ACS) 249th Annual Meeting & Exhibition. Denver, CO. 2015 -Division of Colloid & Surface Chemistry -Symposium: “Advances in Formulations Science & Technology” -Invited Symposium Speaker Presentation: "Advances in Targeted Multifunctional Inhalation Aerosols with Nanotechnology and Solid-State Particle Engineering Design”
• Mansour, H. M. (2015, Spring). Multifunctional Nanotechnology in Lung Surfactant-Mimic Inhalation Aerosols as High-Performing Dry Powder Inhalers for Targeted Pulmonary Medicine.. American Thoracic Society (ATS) International Conference/ISAM joint conference,. Denver, CO.: The American Thoracic Society (ATS).
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  Mansour, H.M. Multifunctional Nanotechnology in Lung Surfactant-Mimic Inhalation Aerosols as High-Performing Dry Powder Inhalers for Targeted Pulmonary Medicine. 2015 American Thoracic Society (ATS) International Conference/ISAM joint conference, Denver, CO. (May 2015). American Journal of Respiratory & Critical Care Medicine (2015) 191: A5030. (Impact Factor: 12.996)
• Mansour, H. M. (2015, Spring). Survival in Advanced CF and Non-CF Bronchiectasis.. American Thoracic Society (ATS) International Conference. Denver, CO.: The American Thoracic Society (ATS).
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  Hayes, D. Jr, Black, S.M., Kirkby S, Kopp B, Tobias, J.D., Mansour, H.M., and Whitson, B.A. Survival in Advanced CF and Non-CF Bronchiectasis. 2015 American Thoracic Society (ATS) International Conference, Denver, CO. (May 2015). American Journal of Respiratory & Critical Care Medicine (2015) 191: A2447. (Impact Factor: 12.996)
• Mansour, H. M. (2015, summer). Translating Lung Surfactant Biophysics, Nanotechnology, and Nrf2 Pathway to Advanced Dry Powder Inhalation Medicine.. Gordon Research Conference on Lung Biology, Injury, and Repair: Translating Lung Biology to Respiratory Medicine.. NH: Gordon Research Conferences.
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  Mansour, H.M. and Hayes, D. Jr. Translating Lung Surfactant Biophysics, Nanotechnology, and Nrf2 Pathway to Advanced Dry Powder Inhalation Medicine. 2015 Gordon Research Conference on Lung Biology, Injury, and Repair: Translating Lung Biology to Respiratory Medicine. NH. (August 2015)
• Muralidharan, P., Hayes, Jr., D., & Mansour, H. M. (2015, fall). Physicochemical Characterization and Aerosol Dispersion Performance of Microparticulate/Nanoparticulate Inhalable Powders of a Novel Nrf2 Activator for COPD Treatment. Priya Muralidharan (graduate student presenter),. AAPS Annual Meeting & Exhibition. Orlando, FL: AAPS.
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  Physicochemical Characterization and Aerosol Dispersion Performance of Microparticulate/Nanoparticulate Inhalable Powders of a Novel Nrf2 Activator for COPD Treatment. Priya Muralidharan (graduate student presenter), Don Hayes, Jr., and Heidi M. Mansour. AAPS Annual Meeting & Exhibition, Orlando, FL. (October 2015). Poster R6034. Travel grant award recipient by The UA Graduate and Professional Student Council.
• Mansour, H. M. (2014, April). Invited Faculty Instructor-Designing High Performing Microparticulate/Nanoparticulate Dry Powder Inhalers by Organic Solution Advanced Spray Drying. Buchi Advanced Spray Drying Hands-On Course. Delaware: Buchi US Headquarters.
• Mansour, H. M. (2014, Spring). Invited SpeakerResearch Presentation Title: "Nanotechnology and Particle Engineering Design for Targeted Pulmonary Delivery in Lung Cancer". UA NCI Comprehensive Cancer Center Grand Rounds. Tucson, AZ: The UA NCI CCC.
• Mansour, H. M. (2014, spring). Advances in Nanotechnology Research for Targeted Pulmonary Disease Treatment and Prevention-Invited Speaker. Meijo University (Japan) Visiting Pharmacy Students & Visiting ProfessorsThe UA COP Internationa Program & Meijo University.

Poster Presentations

• Abrahamson, M., Acosta, M. F., Black, S., & Mansour, H. M. (2020, May/Spring). In Vitro Aerosol Dispersion Performance of Dry Powder Inhalable Particles of Metformin Using Different FDA-Approved Human Dry Powder Inhaler Devices.. Senior Research Project Symposium. Tucson: The UA.
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  Oral e-Poster presentation
• Alabsi, W., Polt, R., & Mansour, H. M. (2020, April/Spring). Physiochemical Characterization of Peptides and Glycopeptides Dry Powders for Intranasal (IN) Delivery to Bypass the Blood Brain Barrier (BBB) and Target the Brain.. Women in Data Science-Tucson's Virtual Conference. Tucson: The UA.
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  Oral presentation with e-poster
• Alabsi, W., Polt, R., & Mansour, H. M. (2020, July/Summer). Physicochemical Characterization of Organic Solution Advanced Spray-Dried Microparticulate/Nanoparticulate Dry Powder of Lactomorphin (MMP-2200) for Intranasal Delivery to Target the Brain by Bypassing the Blood-Brain Barrier for Pain Relief. 2020 Controlled Release Society (CRS) International Annual Meeting, Exposition, & Virtual Conference. New York: Controlled Release Society.
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  Oral presentation with e-poster
• Encinas-Basurto, D., Black, S., & Mansour, H. M. (2020, July/Summer). Advanced Co-Spray Dried Proliposomes for Targeted Pulmonary Delivery as Inhalation Aerosols in Pulmonary Hypertension.. 2020 Controlled Release Society (CRS) International Annual Meeting, Exposition, & Virtual Conference. Las Vegas, NV: The Controlled Release Society.
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  Oral e-Poster presentation
• Fazel, M. T., Mansour, H., Benjamin, A., Cooley, J. H., & Cameron, C. K. (2020, July 2020). Implementing a culture of professional identity formation through intentional career pathways reflection and aligned mentorship. AACP Annual Meeting. Online: AACP.
• Rendon, J., Ruiz, V., & Mansour, H. M. (2020, August/Summer). Predicting Chemical, Physical, and Pharmacokinetic Properties of Drugs that Treat Insomnia using Molecular Modeling.. UAHS BLAISER Program Research Symposium. Tucson: SVP Office, UAHS.
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  Oral and Poster presentations
• Robida, O., & Mansour, H. M. (2020, May/Spring). Predictive Modeling of Physicochemical and Pharmacokinetic Properties of Drugs.. The Honors College Research Symposium. Tucson: The UA.
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  Oral and Poster presentations
• Abrahamason, M., Acosta, M. F., Black, S. M., & Mansour, H. M. (2019, December). In Vitro Aerosol Dispersion Performance of Dry Powder Inhalable Partcles of Metformin Using Different FDA-Approved Human Dry Powder Inhaler Devices. ASHP MIdyear Conference, NV. Las Vegas, NV: ASHP.
• Alabsi, W., Apostol, C., Hanrahan, D., Jaynes, T., Marciniak, A., Szabo, L., Polt, R., & Mansour, H. M. (2019, July/summer). Glycopeptides as Drug Candidates for Brain Delivery and as Dry Powder Inhaler for Intranasal Delivery to Bypass the Blood Brain Barrier (BBB). American Association of Pharmaceutical Scientists (AAPS) Rocky Mountain West, Hillsboro, OR. Hillsboro, OR: AAPS (American Association of Pharmaceutical Scientists).
• Bansback, K., & Mansour, H. M. (2019, April). Molecular Modeling of Drugs for Prediction of Their Physical, Chemical, and Biological Properties. The UA Honor's College Research Symposium.
• Bautista, C., Encinas-Basurto, D., Valenzuala, B., Vallorz, E., Blohm-Mangone, K., Schnellmann, R. G., & Mansour, H. M. (2019, August). Synthesis and Physicochemical Analysis of PLGA-Based Nanoparticles for Drug Delivery. NIH BUILD Scholars Research Conference & Colloquium, The UA Graduate College, Office of Diversity & Inclusivity. Tucson, AZ: NIH BUILD Scholars Research Grant Program & The UA Graduate College.
• Bautista, C., Encinas-Basurto, D., Valenzuala, B., Vallorz, E., Blohm-Mangone, K., Schnellmann, R. G., & Mansour, H. M. (2019, Nov). Synthesis and Physicochemical Analysis of PLGA-Based Nanoparticles for Drug Delivery. Annual Biomedical Research Conference for MInority Students (ABRCMS), Anaheim, CA. Anaheim, CA: ABRCMS.
• Bautista, C., Encinas-Basurto, D., Valenzuala, B., Vallorz, E., Blohm-Mangone, K., Schnellmann, R. G., & Mansour, H. M. (2019, September). Synthesis and Physicochemical Analysis of PLGA-Based Nanoparticles for Drug Delivery. NIH BUILD Scholars Symposium, TX. The Univ of Texas-El Paso, El Paso, TX.: The National Institutes of Health (NIH).
• Miller, A. J., Smith, R. T., Woods, N. M., Vallorz, E., Mansour, H. M., & Myrdal, P. M. (2019, April). Project Mexico: a cross-border analysis of medication content. UA COP Senior Research Project Symposium. Tucson, AZ: UA COP Senior Research Project Symposium.
• Valenzuala, B., Encinas, D., Bautista, C., Vallorz, E., Blohm-Mangone, K., Schnellmann, R. G., & Mansour, H. M. (2019, August). Design of PLGA Nanoparticles and Their Properties for Effective Drug Delivery. The BLAISER Research Symposium/SVP Office UAHS/UROC-MHD UA Graduate College Office of Diversity & inclusivity. Tucson, AZ: SVP Office UAHS/UROC-MHD UA Graduate College Office of Diversity & inclusivity.
• Zhang, L., Liu, F., Acosta, M., Schnellmann, R. G., Mansour, H. M., & Kirkwood, K. (2019, June/summer). Topical Suramin Diminishes Radiation-Induced Oral Mucosistis. International Association of Dental Research (IADR), Vancouver, Canada. Vancouver, Canada: International Association of Dental Research (IADR).
• Acosta, M. F., Hayes, D., Fineman, J. R., Black, S. M., & Mansour, H. M. (2018, February/spring). Dry Powder Inhalers for the Treatment of Pulmonary Hypertension. Graduate & Professional Student Council (GPSC) Student Showcase 2018. Tucson, AZ: The UA Graduate & Professional Student Council (GPSC).
• Acosta, M. F., Hayes, D., Fineman, J. R., Black, S. M., & Mansour, H. M. (2018, July/Summer). Targeted delivery of Simvastatin as Dry Powder Inhaler for the Treatment of Pulmonary Hypertension. 45th Annual Controlled Release Society Annual Meeting & Exhibition. New York: Controlled Release Society.
• Sears, S., Acosta, M. F., Tang, H., Klinger, C., Yuan, J. X., Mansour, H., & Black, S. M. (2018, May/Spring). Inhaled L-Carnitine Attenuates the Development of Pulmonary Arterial Hypertension in Rats. American Thoracic Society (ATS) Conference & Exhibition. San Diego: ATS.
• Acosta, M. F., Hayes Jr, D., Fineman, J. R., Black, S. M., & Mansour, H. M. (2017, July). Dry Powder Inhalers of a Uniform Drug Composition of Simvastatin and L-Carnitine for the Treatment of Pulmonary Hypertension.. 44th Annual Controlled Release Society (CRS) International Annual Meeting & Exhibition. Boston, MA: Controlled Release Society (CRS).
• Gomez, A. I., Acosta, M. F., Hayes Jr, D., & Mansour, H. M. (2017, July). Solid State Liposomes of Amphotericin B for the Targeted Treatment of Pulmonary Fungal Infections.. 44th Annual Controlled Release Society (CRS) International Annual Meeting & Exhibition. Boston, MA: Controlled Release Society (CRS).
• Malapit, M., Mallory, E. K., Muralidharan, P., Phan, H., Hayes, D., & Mansour, H. M. (2017, May). In Vitro Aerodynamic Analysis of Co-Spray Dried Fluticasone Propionate (FP) and Salmeterol Xinofoate (SX) Dry Powder Inhalation Aerosols with Lactose-Alternative Excipient.. UA COP Senior Project Research Day. Tucson, AZ: UA COP.
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  UA COP Senior Project Research Day
• Mallory, E. K., Malapit, M., Muralidharan, P., Phan, H., Hayes, D., & Mansour, H. M. (2017, May). In Vitro Aerodynamic Analysis Of Co-Spray Dried Fluticasone Propionate (fp) And Salmeterol Xinafoate (sx) Dry Powder Inhalation Aerosols With Lactose-Alternative Excipient. The ISAM (Int'l Soc of Aerosols in Medicine) conference at American Thoracic Society (ATS) International Annual Conference & Exhibition.. Washington, D.C.: ATS & ISAM.
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  invited poster presentation authored by my graduate students, PharmD students, PhPr faculty colleague, COM colleague, and myself.The ISAM conference day joint with the ATS conference
• Muralidharan, P., Hayes Jr, D., Black, S. M., & Mansour, H. M. (2017, July). Novel Dry Powder Inhaler containing the Nrf2 Activator Dimethyl Fumarate – Particle Engineering Design, Development and In Vitro Aerosol Dispersion Performance.. 44th Annual Controlled Release Society (CRS) International Annual Meeting & Exhibition. Boston, MA: Controlled Release Society (CRS).
• Muralidharan, P., Malapit, M., Mallory, E. K., Hayes Jr, D., & Mansour, H. M. (2017, July). Solid State Characterization of Carrier-Free Formulation of Fluticasone Propionate and Salmeterol Xinafoate Dry Powder Inhaler. 44th Annual Controlled Release Society (CRS) International Annual Meeting & Exhibition. Boston, MA: Controlled Release Society (CRS).
• Acosta, M. F., Gomez, A. I., Hayes Jr, D., & Mansour, H. M. (2016, November). Advanced Spray-Dried Inhalable Proliposomes of Amphotericin B for the Treatment of Fungal Infections.. AAPS Annual Meeting & Exhibition,. Denver, CO: American Association of Pharmaceutial Scientists (AAPS).
• Acosta, M. F., Hayes Jr, D., Fineman, J. R., Black, S. M., & Mansour, H. M. (2016, November). Design, Physicochemical Characterization and Aerosol Dispersion Performance of Simvastatin and L-Carnitine Microparticles/Nanoparticles for the Treatment of Pulmonary Hypertension.. AAPS Annual Meeting & Exhibition,. Denver, CO: American Association of Pharmaceutial Scientists (AAPS).
• Gomez, A. I., Acosta, M. F., & Mansour, H. M. (2016, February). Advanced Spray Dried Proliposomes as Dry Powder Inhaler: An Advanced Drug Delivery System for Pulmonary Administration.. NSF LSAMP National Research Symposium,. Baltimore, Maryland: The NSF (National Science Foundation) LSAMP (Louis Stokes Alliance for Minority Participation).
• Grijalva, C., Pina, A., Acosta, M. F., Gomez, A. I., Muralidharan, P., Hayes Jr, D., Black, S. M., & Mansour, H. M. (2016, August). Comparison of the In Vitro Aerosol Dispersion Performance of a Nrf2 Activator Using Two Different Human Dry Powder Inhaler Devices.. UA UROC STAR Research Conference & Colloquium, The UA Graduate College. Tucson, AZ: The UA Graduate College.
• Malapit, M., Mallory, E., Muralidharan, P., & Mansour, H. M. (2016, December). In Vitro Aerodynamic Analysis of Co-Spray Dried Fluticasone Propionate (FP) and Salmeterol Xinofoate (SX) with Lactose Alternative Excipient. ASHP Midyear Clinical Meeting & Exhibitio. Las Vegas, NV: ASHP.
• Muralidharan, P., Hayes Jr, D., Black, S. M., & Mansour, H. M. (2016, July). Novel Dry Powder Inhaler containing the Nrf2 Activator Dimethyl Fumarate – Particle Engineering Design, Development and In Vitro Aerosol Dispersion Performance.. 43th Annual Controlled Release Society (CRS) Meeting & Exhibition. Seattle, WA: Controlled Release Society (CRS).
• Pina, A., Grijalva, C. L., Acosta, M. F., Gomez, A. I., Muralidharan, P., Hayes Jr, D., Yuan, J. X., Black, S. M., & Mansour, H. M. (2016, September). Improvement of In Vitro Aerosol Dispersion Performance by Using Mannitol as Part of a Dry Powder Inhaler Formulation.. NIH BUILD Scholars Symposium. The Univ of Texas-El Paso, El Paso, TX.: The National Institutes of Health (NIH).
• Pina, A., Grijalva, C., Acosta, M. F., Gomez, A. I., Muralidharan, P., Hayes Jr, D., Yuan, J. X., Black, S. M., & Mansour, H. M. (2016, August). Improvement of In Vitro Aerosol Dispersion Performance by Using Mannitol as Part of a Dry Powder Inhaler Formulation.. NIH BUILD Scholars Research Conference & Colloquium, The UA Graduate College,. Tucson, AZ: NIH BUILD Scholars Research Grant Program & The UA Graduate College.
• Stocke, N. A., Arnold, S., Mansour, H. M., & Hilt, J. Z. (2014, April). Inhalable Magnetic Nanocomposite Microparticles (MnMs) Dry Powders for Targeted Pulmonary Delivery.. 2014 Society for Biomaterials (SFB) Annual Meeting & Exhibition. Denver, CO.
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  Inhalable Magnetic Nanocomposite Microparticles (MnMs) Dry Powders for Targeted Pulmonary Delivery. 2014 Society for Biomaterials (SFB) Annual Meeting & Exhibition, Denver, CO. (April 2014) Poster 422.
• Stocke, N. A., Arnold, S., Mansour, H., & Hilt, J. Z. (2014, September). Inhalable Nanocomposites for Targeted Pulmonary Delivery and Applications in Lung Cancer Therapy.. 2014 Globalization of Pharmaceutics Education Network (GPEN) Annual Meeting. Helsinki, Finland.
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  Inhalable Nanocomposites for Targeted Pulmonary Delivery and Applications in Lung Cancer Therapy. 2014 Globalization of Pharmaceutics Education Network (GPEN) Annual Meeting, Helsinki, Finland, Europe. (September 2014). 1st Place-Best Poster Presentation Award to Grad Student, Nathanael Stocke, whom I co-advise

Creative Productions

• Mansour, H. M. (2017. Co-Chair: New Session on Drug Delivery & Nanotechnology at the 10th International Conference Neonatal & Childhood Pulmonary Vascular Disease. 10th International Conference Neonatal & Childhood Pulmonary Vascular Disease. San Francisco, CA: UCSF COM. http://www.ucsfcme.com/2017/MPD17002/info.html
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  10th International Conference Neonatal & Childhood Pulmonary Vascular Disease