Novel mucoadhesive PLGA-PVM/MA micro-nanocomposites loaded with felodipine intended for pulmonary administration by nebulization

Poly(latic-co-glycolic) acid (PLGA) nanoparticles loaded with felodipine (FEL) were embedded in a mucoadhe-sive matrix of poly (methyl vinyl ether-co-maleic anhydride) (PVM/MA) to prepare micro-nanoparticulate composites by particle engineering. Composites were characterized for physical and rheological properties and formulated with inhalable grade lactose. In-vitro characterization studies such as drug release kinetics, and mucoadhesive, and aerodynamic properties were performed. The in-vivo efficacy was evaluated by administering the optimized composites by nebulization in hypertensive rats. The obtained FEL-PLGA-PVM/MA composites of 1,069 +/- 82 nm showed sustained drug release and mucoadhesive properties. Bulk and tapped densities of composites mixed with lactose were 0.08-0.13 g/mL and 0.18-0.30 g/mL, respectively, with mass median aerodynamic diameters (MMAD) in a range of 1.29-12.0 mu m. After pulmonary administration of the composites, a decrease in systolic and diastolic blood pressure was observed within the first 3 h, of-9.0 +/- 1.3 % and-13.9 +/- 3.3 %, respectively, with a maximal effect at 12 h (sustained during 144 h), in contrast to pure FEL, which showed no significant decrease in blood pressure (1.6 +/- 2.7 % and 4.1 +/- 4.1 %). Findings suggest that novel mucoadhesive FEL-PLGA-PVM/MA composites are a promising strategy formulation to treat systemic diseases by pulmonary route.