Optimization of brain targeted chitosan nanoparticles of Rivastigmine for improved efficacy and safety.

ABSTRACT

The study aims at formulation and optimization brain targeted nanoparticles (NP) of Rivastigmine (RT) to improve its therapeutic potential and to verify its safety profile. The NP were optimized using a two factor three level (3(2)) central composite design aiming to minimize particle size; maximize zeta potential and drug entrapment efficiency of NP. The optimized formulation (cRTNP) was evaluated using in vitro drug release study; in vivo behavioral, and biochemical and maximum tolerated dose (MTD) study. The optimized formulation evidenced a significant reversal of scopolamine-induced amnesia by Tween 80(®) coated nanoparticles as compared to both pure RT as well as uncoated nanoparticles. The MTD of RT was increased by 10% by formulating them as cRTNP. Thus, formulation of RT as cRTNP improved the therapeutic and safety profile of RT.