Topical delivery of pluronic F127/TPGS mixed micelles-based hydrogel loaded with glycyrrhizic acid for atopic dermatitis treatment

Abstract

Objective

The purpose of this study was to develop pluronic F127/d-a-tocopheryl polyethylene glycol 1000 succinate mixed micelles-based hydrogel (MMs-gel) for topical delivery of glycyrrhizic acid (GL) to improve its skin permeability and atopic dermatitis (AD) treatment.

Significance

GL loaded MMs-gel (GL-MMs-gel) could be potentially used as a promising nanocarrier for the treatment of AD.

Methods

GL-MMs were prepared by thin film hydration method and then loaded into carbopol gel. The formulation of GL-MMs-gel was optimized by full factorial design and systematically characterized for drug content, pH, spreadability, in vitro drug release and percutaneous permeation, etc. The therapeutic effect of GL-MMs-gel was also investigated in AD-like skin lesion model in BALB/c mice and compared with GL solution-based gel (GL-sol–gel).

Results

Spherical GL-MMs with particle size of ∼30 nm were successfully incorporated into carbopol gel to form GL-MMs-gel with drug content of (98.80 ± 1.30) %, pH of 6.0 ± 0.08, and spreadability of (7.1 ± 0.2) cm. In vitro drug release profile of GL-MMs-gel exhibited a sustained-release behavior. The permeation flux for GL-MMs-gel (5.15 ± 0.33 µg/cm²/h) was significantly higher than that of GL-sol–gel (3.08 ± 0.34 µg/cm²/h) and GL-MMs-gel increased the accumulative amounts of GL in rats’ skin 8.41 times than GL-sol–gel. The GL-MMs-gel was more effective than GL-sol–gel in suppressions of various AD symptoms including skin lesions, edema, high IgE levels, epidermal hyperplasia, and mast cell infiltration.

Conclusion

All results revealed that MMs-gel could be a promising carrier for topical delivery of GL for the treatment of AD.

Keywords:

• Glycyrrhizic acid
• polymeric mixed micelles
• hydrogel
• skin penetration
• atopic dermatitis
• topical delivery

Disclosure statement

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

Additional information

Funding

This study was financially supported by the Project of Key Laboratory of Traditional Chinese Medicine of Jiangxi Province (Jiangxi Provincial Key Research Laboratory of Clinical Safety Monitoring and Translational Application of Traditional Chinese Medicine Preparations) and National Natural Science Foundation of China [No. 81803741].