Enhancing Antidepressant Effect of Poloxamer/Chitosan Thermosensitive Gel Containing Curcumin-Cyclodextrin Inclusion Complex

摘要

Poor solubility and bioavailability are limiting factors for the clinical application of curcumin. This study seeks to develop poloxamer/chitosan thermosensitive gel containing curcumin-cyclodextrin inclusion complex with enhanced brain bioavailability and antidepressant effect. The optimized gel had shorter gelation time and produced sustained release in vitro characterized with non-Fickian diffusion. Pharmacokinetics of gel were evaluated using male Sprague-Dawley rats receiving 240 mu g/kg of curcumin and curcumin-cyclodextrin inclusion complex through intranasal administration, compared against a control group receiving intravenous curcumin (240 mu g/kg). The intranasal administration of gel provided sustained release by maintaining plasma concentrations of curcumin above 21.27 +/- 3.26 ng/mL for up to 8 h. Compared to intranasal administration of the inclusion complex, AUC(0-8 h) of curcumin from thermoreversible gel in plasma and hippocampus was increased 1.62- and 1.28-fold, respectively. The gel exhibited superior antidepressant activity in mice. The findings reported here suggested that the clinical application of curcumin can be better exploited through an intranasal administration of the thermosensitive gel.