Ascorbic acid tethered polymeric nanoparticles enable efficient brain delivery of galantamine: An in vitro-in vivo study

The aim of this work was to enhance the transportation of the galantamine to the brain via ascorbic acid grafted PLGA-b-PEG nanoparticles (NPs) using SVCT2 transporters of choroid plexus. PLGA-b-PEG copolymer was synthesized and characterized by (1)H NMR, gel permeation chromatography, and differential scanning calorimetry. PLGA-b-PEG-NH(2) and PLGA-b-mPEG NPs were prepared by nanoprecipitation method. PLGA-b-PEG NPs with desirable size, polydispersity, and drug loading were used for the conjugation with ascorbic acid (PLGA-b-PEG-Asc) to facilitate SVCT2 mediated transportation of the same into the brain. The surface functionalization of NPs with ascorbic acid significantly increased cellular uptake of NPs in SVCT2 expressing NIH/3T3 cells as compared to plain PLGA and PLGA-b-mPEG NPs. In vivo pharmacodynamic efficacy was evaluated using Morris Water Maze Test, Radial Arm Maze Test and AChE activity in scopolamine induced amnetic rats. In vivo pharmacodynamic studies demonstrated significantly higher therapeutic and sustained action by drug loaded PLGA-b-PEG-Asc NPs than free drugs and drug loaded plain PLGA as well as PLGA-b-mPEG NPs. Additionally, PLGA-b-PEG-Asc NPs resulted in significantly higher biodistribution of the drug to the brain than other formulations. Hence, the results suggested that targeting of bioactives to the brain by ascorbic acid grafted PLGA-b-PEG NPs is a promising approach.