Design Development and Evaluation of Nanoformulation for Brain Targeting and Bioavailability enhancement of anti viral drug

Abstract

newline HIV infections causing AIDS is one of the most life-threatening infections and is the sixth leading cause of death. The non-nucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections are reported to have low bioavailability pertaining to high first pass metabolism, high protein binding and enzymatic metabolism. They also show low permeability across blood brain barrier. The central nervous system is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective to provide increased permeability and protection to drug by biocompatible lipidic content and nano-scale size, and thus to develop formulation having potential for enhanced bioavailability and brain targeting. Solid lipid nanoparticles (SLN) were prepared by high pressure homogenization technique using a systematic approach of design of experiments and evaluated for particle size, polydispersity index (PDI), zeta potential and entrapment efficiency. Particles of average size 108.5 nm having PDI of 0.172 with 64.9% entrapment efficiency were produced. Zeta potential was found to be -21.2 mV and the formulation was found stable. Transmission electron microscopic evaluation and the histopathological studies respectively indicated spherical shape and non-irritant nature of the formulated solid lipid nanoparticles. The optimized SLN were incorporated in thermo-sensitive in-situ gelling system. The efavirenz SLN based gel was evaluated for various parameters like gelation temperature, pH, viscosity, transmittance, mucoadhesive strength, spreadability, in-vitro and ex-vivo release studies. The release of drug was found to best fit in the Zero order release kinetics (R2 = 0.9873), indicating concentration independent diffusion controlled release. The in vivo pharmacokinetic studies revealed increased concentration of the drug in brain, when administered through intranasal route indicating its potential for an attempt towards complete eradi