Pharmacokinetic profile of chitosan modified poly lactic co-glycolic acid biodegradable nanoparticles following oral delivery of gentamicin in rabbits

Abstract

Gentamicin (GM) is a well know antibiotic and drug of choice for various infections and is available in the form of parenteral and topical formulations. Gentamicin has no oral dosage form due to its enzymatic degradation and poor bioavailability. This study was designed to optimize controlled release oral dosage form of GM using poly lactic co-glycolic acid (PLGA) nanoparticles (NPs) which were surface modified with chitosan. Nanoparticles were characterized for size, potential, scanning electron microscopy and fourier transform infrared spectroscopy. Drug concentration in plasma samples was determined by microbiological assay against Bacillus subtilis (ATCC 9372). In vitro release pattern was studied and the best formulation was administered to healthy rabbits for pharmacokinetic studies. Various pharmacokinetic parameters determined for oral formulation were area under the curve (AUC) 43.2 ± 2.16 h.mg/L, volume of distribution (Vd) 1.54 ± 0.25 L, half-life phase-1 (t1/2α) 0.59 ± 0.12 h, mean residence time (MRT) 11.22 ± 0.42 h, time to reach maximum concentration (Tmax) 2.56 ± 0.09 h and maximum concentration (Cmax) was 3.49 ± 0.10 mg/L. It is concluded that chitosan modified GM loaded PLGA NPs has potential for oral absorption and can be used for achieving therapeutic benefits.