DEVELOPMENT AND CHARACTERIZATION OF PLGA-CHITOSAN-PEG BLENDED POLYMERIC NANOPARTICLES FOR BRAIN TARGETING OF AN ANTIPSYCHOTIC AGENT FOLLOWED BY ORAL ADMINISTRATION.

摘要

The present investigation was to develop PEGylated poly (lactic-co-glycolic acid) (PLGA) based nanoparticles (PNPs) of Zotepine and to evaluate the brain targeting efficacy following oral administration. Zotepine loaded PNPs were formulated by solvent evaporation technique and were characterized. Stability study was carried out for 3 months. In-vivo study was carried out to ascertain the brain targeting property. Optimal Zotepine loaded PNPs containing ] 00 mg Zotepine, 0.2% w/v of PLGA, 30 mg Chitosan, 25 mg PEG-2000 and 2% PVA was found to be stable with 165.32�3.42 nm, -16.5 �2.86 mV and 73.4+2.71 % as average particle size, zeta potential and % entrapment efficiency (% EE) respectively. TEM result confirmed the size distribution and morphology. PEGytation was confirmed through FT-1R, C13 NMR and 1H NMR study. Comparative in-vitro drug release study showed relatively more sustained release of drug for fabricated formulation than that of marketed formulation. Based on kinetic modeling, the drug release data fit well to Higuchi equation (r2=0.927) indicating the diffusion rate limited drug permeation. Ex-vivo permeation study revealed the rapid permeation which in-tern due to smaller particle size compared to NPs. Higher % DTE of formulation to that of marketed formulation and uncoated PLGA NPs reveal the rapid brain uptake following oral administration which may be due to reduction in the over expression of P-gp mediated efflux mechanism at BBB and its long circulating property. Data of the present study revealed that developed formulation may represent a significant and alternative drug delivery carrier for schizophrenia treatment.