Sustained release nanoparticulate formulation containing antioxidant-ellagic acid as potential prophylaxis system for oral administration.

摘要

The aim of the present work was to develop ellagic acid (EA) loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for oral administration. PLGA nanoparticles were prepared by a method based on the concept of emulsion-diffusion-evaporation by using polyethylene glycol (PEG) 400 as a cosolvent for solubilizing the drug. While developing this method, didodecyldimethylammomium bromide (DMAB) and polyvinyl alcohol (PVA), alone and in combination with chitosan (CS) were employed. DMAB stabilized particles were the smallest of all the formulations with a particle size of 148.5 nm. PVA alone gave particles of 269.7 nm but a blend with CS (80:20) resulted in an increase in particle size (359.6 +/- 23.6 nm). Initial release of EA from nanoparticles in pH 7.4 phosphate buffer was rapid, followed by a slower sustained release. Release rates followed the order PVA > PVA-CS > DMAB. Release rate from the PLGA-DMAB particles was slowest, which is attributed to higher hydrophobicity of DMAB as compared to PVA, preventing diffusion of drug out of polymeric matrix. Insolubility of CS at alkaline pH could have retarded the release in case of PVA-CS system. In situ intestinal permeability study of pure drug and the drug encapsulated in nanoparticles prepared using PVA, PVA-CS blend and DMAB as stabilizer in rats showed 66, 75, 73 and 87% permeation, respectively. EA showed good free radical scavenging effect in a yeast cell culture model as well as in a cell free system.