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

作者：Kunda Nitesh K; Alfagih Iman M; Dennison Sarah R; Somavarapu Satyanarayana; Merchant Zahra; Hutcheon Gillian A; Saleem Imran Y^*

来源：International Journal of Pharmaceutics, 2015, 492(1-2): 213-222.

DOI：10.1016/j.ijpharm.2015.07.015

• Dry powder inhalation
• Nanoparticles
• Pulmonary delivery
• Spray drying
• Proteins

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 mu g 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 Buchi-290 mini-spray dryer to produce nanocomposite microparticles (NCMPs) containing cationic NPs. The aerosol properties showed a fine particle fraction (FPF, dae < 4.46 mu m) of 70.67 +/- 4.07% and mass median aerodynamic diameter (MMAD) of 2.80 +/- 0.21 mu m 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 mu g/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.

• 出版日期2015-8-15