ACYCLOVIR LOADED GELATIN BIODEGRADABLE NANOPARTICLES: FORMULATION, OPTIMIZATION, CHARACTERIZATION, AND IN-VIVO EVALUATIONAbstract
Acyclovir has a ratified antiretroviral effect for Herpes simplex virus type 1 (HSV-1), HSV-2, Varicella zoster virus (VZV), Herpesvirus simiae and to a minor extent, Epstein-Barr virus (EBV). The oral bioavailability of acyclovir is indigent, with only 15%–30% of the oral formulations’ vitality absorbed. To baffle the issue of insignificant bioavailability, acyclovir was formulated into biodegradable gelatin nanoparticles through a double desolvation method adopting gelatin, acetone as desolvating agent, and glutaraldehyde as a cross-linking agent. Optimization was imposed through design expert software whereby the aftermath of gelatin polymer concentration (X1) and glutaraldehyde-crosslinking agent (X2) was studied on particle size (Y1), zeta potential (Y2) and entrapment efficiency (Y3). The optimized formulation (F9) demonstrated a particle size, zeta-potential and maximum entrapment efficiency of 139.87 nm -32.67mv and 91.23%, respectively. The rate of drug release from acyclovir-loaded gelatin nanoparticles ensued from first-order kinetics, and Korsmeyer-peppas plots established the mechanism of drug release from nanoparticles. The release exponent (n) value indicating that drug release embellished by quasi-fickian diffusion transport. The in-vivo pharmacokinetic parameters such as maximum plasma concentration (Cmax) (4.6 ng/ml), time for peak plasma concentration (tmax) (60 min), plasma half life (t1/2) (508 min) mean residence time (MRT)(479.8 min), area under curve (AUC0-α) ( 941.93 ng/ml.min) and AUMC(451931.6921) of optimized formulation showed better results than pure drug and marketed formulation. The relative bioavailability of acyclovir was increased about three-fold after gelatin nanoparticles administration as compared to pure drugs.