Surfactant-free, biodegradable nanoparticles for aerosol therapy based on the branched polyesters, DEAPA-PVAL-g-PLGA

Purpose. This study describes the development of surfactant-free, biodegradable nanoparticle systems with varying physicochemical properties and their suitability for pulmonary application via nebulization. Methods. Nanoparticle suspensions were formulated from the branched polyester, diethylaminopropyl amine-poly( vinyl alcohol)grafted-poly( lactide-co-glycolide) (DEAPA-PVAL-g-PLGA) alone, as well as with increasing amounts of carboxymethyl cellulose (CMC). Particle size, zeta potential, turbidity, and morphology ( atomic force microscopy) were characterized. Three formulations were chosen for further study: Cationic nanoparticles without CMC, cationic nanoparticles with CMC, and anionic nanoparticles with an excess of CMC. Nanoparticle degradation was characterized, as well as stability during nebulization. Nanoparticle-cell interactions were investigated and quantified using confocal laser scanning microscopy and fluorescence spectrometry. Results. Nanoparticles ranged in size from 70 - 250 nm and displayed zeta potentials of + 58.9 to - 46.6 mV. Anionic nanoparticles showed the highest stability during nebulization. The degradation rate of each nanoparticle formulation decreased with increasing amounts of CMC. Cell association was highest among cationic nanoparticles (57% and 30%, respectively), although these were not internalized. Despite a lower rate of cell association (3%), anionic nanoparticles were internalized by A549 cells. Conclusions. Surfactant-free nanoparticles from DEAPA-PVAL-g-PLGA are versatile drug delivery systems; however, only the anionic formulations investigated were proven suitable for aerosol therapy.