The transdermal performance, pharmacokinetics, and anti-inflammatory pharmacodynamics evaluation of harmine-loaded ethosomes

Abstract

Harmine (HAR) is a β-carboline alkaloid with anti-inflammatory and antipruritic effect. However, the low bioavailability and side effects of HAR severely limited its clinical application. The main objective of this study was to develop harmine-loaded ethosomes (HLE) drug delivery system for topical application to treat inflammation. HLE were obtained by ethanol injection method and characterized. The morphology of HLE was evaluated by transmission electron microscopy (TEM). HLE exhibited a good biocompatibility with human embryonic skin fibroblasts and rat skin. The in vitro skin penetration studies showed that HLE had the greatest skin deposition than harmine-loaded liposomes (HLL) and harmine solution (HS). In vivo pharmacokinetic study demonstrated that AUC_(0–∞) and C_max of HLE in subcutaneous tissues were much higher than that of in blood. Moreover, for convenience of fixing on skin, HLE were mixed with gel. HLE gel significantly inhibited the overexpression of inflammation cytokines prostaglandin E2, interleuking (IL)-1β, nitric oxide, and tumor necrosis factor-alpha (TNF-α) in the inflammation model of rat paw edema compared with HS gel. In short, HLE was promising formulation for topical delivery in treatment of inflammatory diseases.

Keywords:

• Harmine
• ethosomes
• skin deposition
• anti-inflammatory
• pharmacokinetics

Disclosure statement

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

Additional information

Funding

This work was supported by funding from the Key Projects of Joint Funds of the National Natural Science Foundation of China and Xinjiang Uygur Autonomous Region of China [No. U1130303], the National Natural Science Foundation of China [Grant 81872933], the National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program”, China [Grants 2012ZX0910320-051], and the Program of Shanghai Subject Chief Scientist [13XD1403500].