Development of a self-assembled micelles based on cryptotanshinone and glycyrrhizic acid: An efficient strategy for acne treatment

Acne vulgaris is a prevalent inflammatory skin disease affecting the folliculosebaceous unit. Current treatments, such as antibiotics and anti-inflammatory drugs, face challenges like drug resistance and side effects. Cryptotanshinone (CTS), a diterpenoid from Salvia miltiorrhiza, exhibits potential acne-treating effects by inhibiting sebaceous gland secretion, regulating perifollicular keratosis and exhibiting anti-inflammatory properties. However, its poor water solubility and skin permeability hinder clinical application. CTS was researched in the previous work and CTS cerasomes was prepared. However, the issues of low encapsulation rate and large particle size still existed. Here, we propose a strategy for encapsulating CTS using a glycyrrhizin-based carrier to address the issues above. Under microscopic observation, the glycyrrhizic acid-encapsulated CTS micelles (GA-CTS), with an average size of 24.81 +/- 1.40 nm, exhibited a uniform spherical shape. In vitro permeation assay demonstrated that the water solubility and skin permeability of CTS were significantly improved, indicating a higher bioavailability. GA-CTS also inhibited Cutibacterium acnes (C. acnes) and reduced Tumor Necrosis Factor-alpha (TNF alpha) and Interleukin-1(3 (IL-1(3) expression in HaCaT cells. In vivo, a BALB/c mouse acne model was established via intradermal C. acnes injection. HE staining, IL-1(3 immunohistochemistry, and qRT-PCR were used to assess the treatment effect of GA-CTS. Compared to CTS or GA alone, GA-CTS significantly inhibited C. acnes growth, reduced skin swelling, and improved skin histology. Notably, GA-CTS inhibited keratin 16 (K16) gene expression, improving abnormal skin keratinization, and regulated 5-alpha reductase mRNA expression, potentially impacting androgen metabolism and offering another mechanism for acne treatment. In conclusion, GA-CTS micelles show promising potential in acne treatment, offering new insights and methods for anti-acne drug development and clinical application.