Nose to brain delivery of rotigotine loaded chitosan nanoparticles in human SH-SY5Y neuroblastoma cells and animal model of Parkinson's disease

Publication date: Available online 19 February 2020Source: International Journal of PharmaceuticsAuthor(s): Subrat K. Bhattamisra, Angeline S. Tzeyung, Lim Wen Xi, Nurul Hasyanazifa Safian, Hira Choudhury, Lim Wei Meng, Naiyer Shahzad, Nabil A. Alhakamy, Md khalid Anwer, Ammu K. Radhakrishnan, Shadab MdAbstractRotigotine, a non-ergoline dopamine agonist, has been shown to be highly effective for the treatment of Parkinson's disease (PD). However, despite its therapeutic potential, its’ clinical applications were hindered due to low aqueous solubility, first-pass metabolism and low bioavailability. Therefore, we developed rotigotine-loaded chitosan nanoparticles (RNPs) for nose-to-brain delivery and evaluated its neuronal uptake, antioxidant and neuroprotective effects using cell-based studies. The pharmacological effects of nose-to-brain delivery of the RNPs were also evaluated in an animal model of PD. The average particle size, particle size distribution and entrapment efficiency of the RNPs were found to be satisfactory. Exposure of RNPs for 24 hours did not show any cytotoxicity towards SH-SY5Y human neuroblastoma cells. Furthermore, the RNPs caused a decrease in alpha-synuclein (SNCA) and an increase in tyrosine hydroxylase (TH) expression in these cells, suggestion that the exposure alleviated some of the direct neurotoxic effects of 6-OHDA. Behavioral and biochemical testing of RNPs in haloperidol-induced PD rats showed a reversal of catalepsy, akinesia and restorati...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research