Anti-depressant effect of curcumin-loaded guanidine-chitosan thermo-sensitive hydrogel by nasal delivery

Abstract

Curcumin, a polyphenol compound extracted from the roots of turmeric plants, possesses anti-depressant effect by regulating the levels of neuroendocrine immunological factors. The purpose of this study was to investigate the anti-depressant effect of curcumin through nasal delivery. The results of phase solubility, Fourier transform infrared spectra, Differential scanning calorimetry, X-ray powder diffractometry and ¹H NMR spectra assays showed that curcumin/hydroxypropyl-β-cyclodextrin complex had been obtained. The viscosity of hydrogel increased rapidly at the temperature range of 29–30 °C through the test of rheological property of Guanidine-Chitosan thermo-sensitive hydrogel. And the hydrogel had good mucoadhesion properties. The cumulative release rate of curcumin was 55% in 10 h in vitro drug release test. Curcumin-loaded (14.6, 29.2, or 58.4 μg/kg) thermo-sensitive hydrogel could reduce the immobility time of mice in force swimming test and tail suspension test, while could not increase the independent behavioral activity of mice. In addition, curcumin-loaded (14.6, 29.2, or 58.4 μg/kg) thermo-sensitive hydrogel could increase the concentration of Norepinephrine, Dopamine, 5-Hydroxytryptamine and their metabolites in hippocampus and striatum. In conclusion, thermo-sensitive hydrogel delivery system can be seen as a promising formulation of curcumin for the treatment of depression through nasal delivery.

Graphical Abstract

Keywords:

• Curcumin
• hydrogel
• depression
• neurotransmitters
• nasal drug delivery

Acknowledgments

The authors thank professor Yuanlu-Cui, Tianjin University of Traditional Chinese Medicine, for the gracious help in providing Pharmacology laboratory. The authors also acknowledge professor Rui-Shen for her help in analyzing the data and professor Xiaodi-Kou for her help in making a thorough and comprehensive revision on the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [No. 81503461], Natural Science Foundation of Tianjin City [No. 16JCYBJC28000] and Postdoctoral Science Foundation of China [No.2016M591400].