Rivastigmine Loaded PEG-PLGA Nanoparticles for Enhanced Delivery to the Brain: In-Vitro and In-Vivo Studies for Alzheimer’s disease

Abstract Purpose Rivastigmine Tartrate (RT) is a reversible cholinesterase inhibitor used for the treatment of Alzheimer's disease and CNS disorder. The entry of the drug to the brain is restricted is due to the presence of the Blood-Brain Barrier (BBB). In this work, we have developed amphiphilic copolymer, poly (ethylene glycol)-poly (lactide-coglycolide (PEG-PLGA) loaded RT nanoparticles to enhance brain delivery. Methods Rivastigmine-loaded PEG-PLGA nanoparticles were prepared using the nanoprecipitation technique. Pegylated polyethylene glycol (polymer) and Pluronic F68 (Surfactant) were selected as preparation of Polymeric Nanoparticle. Characterization studies on the formulation such as DSC, Zeta potential, SEM, and Drug Entrapment were conducted. In-vitro drug release, Pharmacokinetic, and Pharmacodynamics studies were performed. Results The prepared nanoparticles are spherical and the size ranges from a minimum of 125.93 ± 0.55 to a maximum of 179.60 ± 1.06 nm. In vitro release studies in PBS pH 7.4 showed a biphasic release pattern of the drug from the nanoparticles. Pharmacokinetic studies in male Wistar rats showed an increase in the Cmax of RT when administered as PEG- PLGA nanoparticles than RT administered as a solution in PBS and a notable 3.5fold increase in the T1/2 also was observed. Tissue distribution studies also showed a 4fold increase in the amount of RT as nanoparticles that have entered the brain when compared to RT in PBS. Conclusion The Smaller size of the nanoparticles along with the presence of hydrophilic PEG group has assisted in enhancing the concentration of Rivastigmine in the brain which has consequently even improved the memory learning skills of the animals