Rivastigmine-loaded PLGA and PBCA nanoparticles: Preparation, optimization, characterization, in vitro and pharmacodynamic studies

Sustained release nanoparticulate formulations of Rivastigmine tartrate (RI) were prepared, optimized (using factorial design) and characterized using the biodegradable polymers, PLGA and PBCA as carriers. The pharmacodynamic performances of the nanoparticles (NPs) were evaluated for brain targeting and memory improvement in scopolamine-induced amnesic mice using Morris Water Maze Test. PLGA NPs were prepared by nanoprecipitation technique, while PBCA NPs were prepared by emulsion polymerization technique. Effect of key formulation variables on particle size (PS) and percentage drug entrapment (PDE) of NPs was studied by using factorial design. PLGA NPs showed PS of 135.6 +/- 4.2 nm and PDE of 74.46 +/- 0.76 %, whereas PBCA NPS showed PS of 146.8 +/- 2.6 nm and PDE of 57.32 +/- 0.91%. FTIR and GPC characterization confirmed complete polymerization of n-butyl cyanoacrylate (nBCA) monomer into PBCA. DSC thermograms indicated that RT was dispersed as amorphous state in both PLGA and PBCA NPs. TEM studies indicated that the NPs were spherical. In vitro studies showed 30.86 +/- 2.07% and 43.59 +/- 3.80% release from PLGA and PBCA NPs in 72 h, respectively. Pharmacodynamic study demonstrated faster regain of memory loss in amnesic mice with both PLGA and PBCA NPs when compared to RI solution. This indicates rapid and higher extent of transport of RT into the mice brain and thus shows the suitability of both NPs as potential carriers for providing sustained brain delivery of RT. (C) 2010 Elsevier B.V. All rights reserved.