Evaluation of safety and efficacy of brain targeted chitosan nanoparticles of minocycline

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 100 mg/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 319 mg/kg for MH and 350 mg/kg for cMHNP (350 mg/kg). Thus surface modified nanoparticles (cMHNP) improved the therapeutic efficacy as well as safety of MH.