Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485098 | Journal of Pharmaceutical Sciences | 2010 | 16 Pages |
Abstract
This study was designed to test the feasibility of polymeric microspheres as an inhalable carrier for prostaglandin E1 (PGE1) for treatment of pulmonary arterial hypertension. Poly(lacticâcoâglycolic acid) (PLGA) microspheres were prepared by a double emulsion-solvent evaporation method. Six different microspheric formulations were prepared using two different blends of PLGA (50:50 and 85:15) and varying concentrations of polyvinyl alcohol (PVA) in the external aqueous phase (EAP). The particles were characterized for morphology, size, aerodynamic diameter, entrapment efficiency, release patterns, and metabolic stability. Pulmonary absorption was studied in a rat model, and safety of the formulations was evaluated by measuring cytotoxicity in Caluâ3 cells and assessing injury markers in bronchoalveolar lavage (BAL) fluid. Both actual particle size and aerodynamic diameter of the formulations decreased with increasing PVA concentration. The mass median aerodynamic diameter of the particles was within the respirable range. Entrapment efficiency increased with increasing PVA concentration; PLGA 85:15 showed better entrapment due to hydrophobic interactions with the drug. Compared to intravenously administered PGE1, microspheres prepared with PLGA 85:15 produced a 160âfold increase in the halfâlife of PGE1 following pulmonary administration. Although plain PGE1 showed rapid degradation in rat lung homogenate, PGE1 entrapped in the particles remained intact for about 8âh. Optimized formulations were demonstrated to be safe, based on analysis of cytotoxicity and lungâinjury markers in BAL fluid. Overall, the data suggest that microspheric PGE1 formulations have the potential to be used as a noninvasive and controlledârelease alternative to the current medications used for treatment of pulmonary arterial hypertension that are administered by continuous infusion or require multiple inhalations. © 2009 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1774-1789, 2010
Keywords
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Authors
Vivek Gupta, Amit Rawat, Fakhrul Ahsan,