Pharmaceutical nanotechnologyDry powder pulmonary delivery of cationic PGA-co-PDL nanoparticles with surface adsorbed model protein

Pulmonary delivery of macromolecules has been the focus of attention as an alternate route of delivery with benefits such as; large surface area, thin alveolar epithelium, rapid absorption and extensive vasculature. In this study, a model protein, bovine serum albumin (BSA) was adsorbed onto cationic PGA-co-PDL polymeric nanoparticles (NPs) prepared by a single emulsion solvent evaporation method using a cationic surfactant didodecyldimethylammonium bromide (DMAB) at 2% w/w (particle size: 128.64 ± 06.01 nm and zeta-potential: +42.32 ± 02.70 mV). The optimum cationic NPs were then surface adsorbed with BSA, NP:BSA (100:4) ratio yielded 10.01 ± 1.19 μg of BSA per mg of NPs. The BSA adsorbed NPs (5 mg/ml) were then spray-dried in an aqueous suspension of L-leucine (7.5 mg/ml, corresponding to a ratio of 1:1.5/NP:l-leu) using a Büchi-290 mini-spray dryer to produce nanocomposite microparticles (NCMPs) containing cationic NPs. The aerosol properties showed a fine particle fraction (FPF, dae < 4.46 μm) of 70.67 ± 4.07% and mass median aerodynamic diameter (MMAD) of 2.80 ± 0.21 μm suggesting a deposition in the respiratory bronchiolar region of the lungs.The cell viability was 75.76 ± 03.55% (A549 cell line) at 156.25 μg/ml concentration after 24 h exposure. SDS-PAGE and circular dichroism (CD) confirmed that the primary and secondary structure of the released BSA was maintained. Moreover, the released BSA showed 78.76 ± 1.54% relative esterolytic activity compared to standard BSA.

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