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    The International Society for Aerosols in Medicine

    Fakhrul Ahsan

    Fakhrul Ahsan

    Fakhrul Ahsan

    Texas Tech University Health Sciences Center School of Pharmacy  
    Amarillo, Texas
    USA

    Dr. Fakhrul Ahsan is a University Distinguished Professor in the Department of Pharmaceutical Sciences and Head of the Graduate Program in Pharmaceutical Sciences at the Texas Tech University Health Sciences Center (TTUHSC) School of Pharmacy in Amarillo, Texas. A pharmacist by training, Dr. Ahsan earned his pharmacy degree from the University of Dhaka in Bangladesh and Ph.D. in Pharmaceutics from Complutense University of Madrid. He received his postdoctoral training from the University of Alabama at Birmingham. Dr. Ahsan’s research revolves around the development of novel formulations for the pulmonary delivery of small- and large-molecular-weight therapeutic agents for the treatment of respiratory disorders, including asthma and pulmonary hypertension. Recently, he has diversified his research toward tissue chips for PAH, bioprinting and lung-tissue engineering. He is a member of the Editorial Boards of the European Journal of Pharmaceutical Sciences and the Journal of Pharmacy and Pharmaceutical Sciences, and was an Associate Editor of the Journal of Drug Targeting. He also serves in various NIH and DoD study sections.


    Repurposing rosiglitazone, a PPAR-γ agonist and oral antidiabetic, as an inhaled formulation, for the treatment of PAH

    Abstract
    Peroxisome-proliferator-activated-receptor-gamma (PPAR-γ) is implicated, in some capacity, in the pathogenesis of pulmonary arterial hypertension (PAH). Rosiglitazone, an oral antidiabetic and PPAR-γ agonist, has the potential to dilate pulmonary arteries and to attenuate arterial remodeling in PAH. Here, we sought to test the hypothesis that rosiglitazone can be repurposed as inhaled formulation for the treatment of PAH. We have tested this conjecture by preparing and optimizing poly(lactic-co-glycolic) acid (PLGA) based particles of rosiglitazone, assessing the drug particles for pulmonary absorption, investigating the efficacy of the plain versus particulate drug formulation in improving the respiratory hemodynamics in PAH animals, and finally studying the effect of the drug in regulating the molecular markers associated with PAH pathogenesis. The optimized particles were slightly porous and spherical, and released 87.9%±6.7% of the drug in 24 hours. The elimination half-life of the drug formulated in PLGA particles was 2.5-fold greater than that of the plain drug administered via the same route at the same dose. The optimized formulation, given via the pulmonary route, produced pulmonary selective vasodilation in PAH animals, but oral rosiglitazone had no effect in pulmonary hemodynamics. Rosiglitazone ameliorates the pathogenesis of PAH by balancing the molecular regulators involved in vasoconstriction and vasodilation of human pulmonary arterial endothelial and smooth muscle cells. All in all, data generated using intact animal and cellular models point to the conclusion that PLGA particles of an antidiabetic drug can be used for the treatment of a different disease, PAH.