Polysorbate-80 coated Galantamine-Chitosan nanoparticles for enhanced safety and efficacy: Pharmacokinetics and Brain distribution in Rats

In brain drug delivery, the BBB (Blood-Brain Barrier) has been a great barrier for various active pharmaceutical drugs. Hence, developing suitable drug delivery systems are need of the hour. However, the present study aimed to develop a polysorbate-80 (PS-80) coated galantamine (GAL) loaded chitosan nanoparticles (CS-NPs) with particles less than 200 nm to enhance the drug internalization in the brain. GAL-CS-NPs were prepared using the ionic gelation technique and optimized to obtain a particle size of less than 200nm and further coated wirh PS-80 to obtain polysorbate-80 coated galantamine loaded chitosan nanoparticles (PS-80-GAL-CS-NPs) The physiochemical properties of uncoated GAL-CS-NPs, PS-80 coated GAL-CS-NPs and the in-vitro evaluations, such as cytotoxicity and cellular internalization in SH-SY-5Y human neuroblastoma cell lines, were studied. The particle size of optimized PS-80-GAL-CS-NPs was observed to be 115±4 nm, and zeta potential was found to be 31.2±1.7 mV. While the drug entrapment efficiency was found to be 65.5±1.2 %. The in-vitro drug release of PS-80-GAL-CS-NPs was found to be 56.75±1.3 %. However, the cytotoxicity studies did not show any toxicity for the drug concentrations of 10 and 100 µg/mL. PS-80-GAL-CS-NPs facilitated time-dependent GAL uptake in SH-SY-5Y cell lines. Studies conducted in vivo in plasma revealed a steady release of GAL from PS-80-GAL-CS-NPs. The distribution PS-80- GAL-CS-NPs in the brain after oral administration at 1 ^st , 4 ^th and 8 ^th hr was found to be 1.7, 3.1 and 2.0 folds higher when compared to the uncoated NPs. Further, the histopathological study did not show any morphological changes in the rat brain. This study indicates that PS-80-GAL-CS-NPs might be a promising delivery method for Alzheimer’s Disease (AD)