Self-assembled micelles enhance the oral delivery of curcumin for the management of alcohol-induced tissue injury

Abstract

Curcumin (CUR) shows great potential in the management of alcohol-use disorders. However, the hydrophobicity and poor oral bioavailability result in the limited therapeutic efficacy of CUR against alcohol-induced tissue injury. Here, self-assembled Soluplus® micelles (Ms) were developed for the enhanced oral delivery of CUR. CUR-loaded Soluplus® micelles (CUR-Ms) were prepared using a thin-film hydration method and these micelles displayed nearly spherical shape with an average size of 62.80 ± 1.29 nm. CUR in micelles showed the greater stability, solubility and dissolution than free CUR. With the increased water solubility of CUR-Ms and P glycoprotein inhibition of Soluplus®, the absorption rate constant (Ka) and apparent permeability coefficient (Papp) of CUR-Ms in intestines was respectively 3.50 and 4.10 times higher than that of free CUR. Pharmacokinetic studies showed that CUR-Ms significantly improved the oral bioavailability of CUR. Specifically, the AUC0–∞ and C_max of CUR-Ms were increased by 9.45 and 47.38 folds compared to free CUR, respectively. In mice with alcohol-induced tissue injury, the oral administration of CUR-Ms greatly reduced oxidative stress, and significantly defended liver and gastric mucosa from alcoholic damages. The results demonstrated CUR-Ms with good oral bioavailability could represent a promising strategy for the management of alcohol-induced tissue injury.

Graphical Abstract

Keywords:

• Curcumin
• oral bioavailability
• Soluplus®
• alcoholism
• alcohol-induced tissue injury

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the financial support from the National Natural Science Foundation of China [No. 81603045], the Medical Youth Innovation Research Program of Sichuan Province [No. Q20049], the Major Project of Development and Regeneration Key Lab of Sichuan Province [No. SYS16-005] and the Natural Science Foundation of Chengdu Medical College [No. CYZYB20-11].