FORMULATION, CHARACTERIZATION AND DETERMINATION OF ANTI-ALZHEIMERIC ACTIVITY OF TACRINE LOADED POLY (LACTIDE-CO-GLYCOLIDE) NANOPARTICLES

The objective of this study was to formulate and characterize Tacrine loaded poly (lactide-co-glycolide) (PLGA) nanoparticles used for the treatment of alzheimer’s disease and were prepared by modified nano precipitation method. Pharmacodynamics studies of the nanoparticles were evaluated for brain targeting and memory improvement in scopolamine-induced amnesic mice using Morris water maze test and inhibitory step down avoidance. The nanoparticles were characterized for drug content, particle size and particle morphology using TEM. In-vitro studies were determined by diffusion cells. The particle size of the prepared nanoparticles ranged from 247 nm to 293 nm. Nanoparticles of Tacrine were obtained with entrapment efficiency of 72.34-81.32%. The drug release from the Tacrine nanoparticles was sustained in batch TPGN-3for 24 h with 85.67% drug release. The in-vitro cytotoxicity studies indicate that the IC50 of the Tacrine loaded nanoformulations shown improved in the reduction of the IC50 but plain nanoparticles did not show severe cytotoxicity. In cellular uptake study of the optimized formulation TPGN-3, shows significant intracellular accumulation when compared with pure drug and control. Pharmaco-dynamics study indicates that faster regain of memory in amnesic mice with PLGA nanoparticles when compared to pure drug Tacrine. This study indicates that the higher extent of transport of Tacrine in mice brain and shows improved therapeutic efficacy of Tacrine in the treatment of alzheimer’s disease.