Abstract
Orally administered Sildenafil (SDF) is used to treat pulmonary arterial hypertension. However, it has a relatively low bioavailability of approximately 40%. To circumvent such limitations, pulmonary administration emerges as a promising alternative. This study aimed to develop SDF-loaded porous poly (lactic-co-glycolic acid) microparticles for pulmonary administration. Microparticles were obtained by double emulsion with solvent evaporation, using polyethyleneimine (PEI) as a surfactant and ammonium bicarbonate (ABC) as a porogenic agent. The encapsulation efficiency of microparticles was improved up to ≅86% by using PEI at 1% concentration. Aerodynamic diameter, and tappet density of the optimized formulation (0.5% ABC and 1% PEI) were 4.74 ± 0.09 μm, 0.100 ± 0.002 g.cm−3 respectively. The formulations presented a sustained release for up to 72 h in simulated lung fluid. In the human lung adenocarcinoma A549 cell line, porous Microparticles were non-cytotoxic at a concentration of 384 μg.mL−1 at 72 h of incubation.
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