title: Evaluation of safety and efficacy of brain targeted chitosan nanoparticles of minocycline.
abstract: The aim of present study was to evaluate the antidepressant-like effects of minocycline hydrochloride (MH); enhance this effect using nanoparticulate drug delivery system; and further evaluate their safety by determining maximum tolerated dose (MTD). Pure drug MH, MH loaded nanoparticles (MHNP) and Tween 80(®) coated MH encapsulated nanoparticles (cMHNP) were explored for antidepressant-like activity in terms of immobility period using despair swim test (DST) and tail suspension test (TST) in mice (dose equivalent to 100mg/kg MH, i.p.). For MTD determination, Wistar rats were treated with gradual increasing doses of MH and cMHNP orally for 28 consecutive days and observed for body weight, weight indices (WI), behavioral, biochemical and histopathological changes until MTD was found. In mice, MH treatment showed antidepressant-like activity and cMHNP treatment significantly improved this effect. On the other hand, no significant effect was observed for MHNP treated group. However, administration of MH in any case did not produce locomotor activation, suggesting that the antidepressant-like effects of MH may not be attributed to the enhanced locomotion. The MTD was found to be 319mg/kg for MH and 350mg/kg for cMHNP (350mg/kg). Thus surface modified nanoparticles (cMHNP) improved the therapeutic efficacy as well as safety of MH.
authors.affiliation: Department of Pharmaceutical Sciences, G.J. University of Science and Technology, Hisar 125001, India. kalpananagpal@gmail.com
authors.forename: Kalpana
authors.initials: K
authors.lastname: Nagpal
authors.forename: Shailendra Kumar
authors.initials: SK
authors.lastname: Singh
authors.forename: Dinanath
authors.initials: D
authors.lastname: Mishra
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D048271:Chitosan / Q000737:chemistry*; D003863:Depression / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000138:chemical synthesis*; D004339:Drug Compounding; D004353:Drug Evaluation, Preclinical; D058492:Drug Repositioning; D019417:Hindlimb Suspension; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008911:Minocycline / Q000494:pharmacology*; D008995:Monoamine Oxidase / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D011136:Polysorbates; D051381:Rats; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000928:Antidepressive Agents; D004337:Drug Carriers; D011136:Polysorbates; D048271:Chitosan; D008995:Monoamine Oxidase; D008911:Minocycline