A novel Thermo-responsive hydrogel system (THS) loaded with the active ingredient of Gardenia jasminoides J. Ellis exhibits anti-depressant effects in vivo via intranasal administration

Thermo-responsive hydrogel system (THS) is widely used in biological materials and pharmacy because of their targeting, controlled release and enhanced drug bioavailability. In this work, a novel THS is prepared and optimized from Guanidinylated chitosan (GCS), Poloxamer 407 (P407) and Hydroxypropyl-β-cyclodextrin (HP-β-CD) by single factor and Taguchi orthogonal experiments. The in vitro properties of THS are evaluated by cumulative release, rheology and biocompatibility. Genipin (GP) and Geniposide (GPS), the active ingredient of Gardenia jasminoides J. Ellis are selected as model drugs, and evaluation of anti-depressant effects of GP-THS and GPS-THS via intranasal administration for chronic unpredictable mild stress (CUMS) rats are investigated. In vitro evaluation results of GP-THS and GPS-THS show that both had significant sustained release characteristics, good temperature response and biocompatibility, while the in vivo results exhibit that GP-THS (0.1453, 0.2907, 0.5814 mg/kg), GPS-THS (0.2907 mg/kg) could reduce depressive behavior in CUMS model rats and increase the concentration of 5-Hydroxytryptamine(5-HT), 5-hydroxyindole acetic acid(5-HIAA), Dopamine (DA) and Norepinephrine (NE) in the hippocampus and hypothalamus, displaying better effect than intragastric administration. In conclusion, the THS could become a novel preparation of intranasal administration for brain targeting therapy such as depression.