title: Optimization of brain targeted chitosan nanoparticles of Rivastigmine for improved efficacy and safety.
abstract: The study aims at formulation and optimization brain targeted nanoparticles (NP) of Rivastigmine (RT) to improve its therapeutic potential and to verify its safety profile. The NP were optimized using a two factor three level (3(2)) central composite design aiming to minimize particle size; maximize zeta potential and drug entrapment efficiency of NP. The optimized formulation (cRTNP) was evaluated using in vitro drug release study; in vivo behavioral, and biochemical and maximum tolerated dose (MTD) study. The optimized formulation evidenced a significant reversal of scopolamine-induced amnesia by Tween 80(®) coated nanoparticles as compared to both pure RT as well as uncoated nanoparticles. The MTD of RT was increased by 10% by formulating them as cRTNP. Thus, formulation of RT as cRTNP improved the therapeutic and safety profile of RT.
authors.affiliation: Department of Pharmaceutical Sciences, Guru Jambeshwar University of Science & Technology, Hisar, Haryana 125001, India. kalpananagpal@gmail.com
authors.forename: Kalpana
authors.initials: K
authors.lastname: Nagpal
authors.forename: S K
authors.initials: SK
authors.lastname: Singh
authors.forename: D N
authors.initials: DN
authors.lastname: Mishra
mesh_terms: D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D048271:Chitosan / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000138:chemical synthesis*; D004339:Drug Compounding; D004353:Drug Evaluation, Preclinical; D005163:Factor Analysis, Statistical; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D048448:Phenylcarbamates / Q000494:pharmacology*; D011136:Polysorbates; D051381:Rats; D000068836:Rivastigmine; D012601:Scopolamine; D016896:Treatment Outcome
chemical_list: D004337:Drug Carriers; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D011136:Polysorbates; D048271:Chitosan; D012601:Scopolamine; D000068836:Rivastigmine