Abstract / Summary
Abstract Acne vulgaris is a complex inflammatory disorder, and current treatment options are often limited by antibiotic resistance and cutaneous irritation, underscoring the urgent need for safer multi-target therapeutic alternatives. In this study, a novel antimicrobial cyclic peptide (AMCP) was systematically evaluated for its multidimensional anti-acne efficacy, and a penetration enhancer was developed for improving the topical dermal delivery. At a concentration of 20 µg/mL, AMCP inhibited dihydrotestosterone (DHT)- and linoleic acid (LA)-induced lipid synthesis in SZ95 sebocytes by 40.0% and 29.1%, respectively. Furthermore, it exhibited potent bactericidal activity against C. acnes (MIC or MBC at 0.5 µg/mL) and S. aureus (MIC or MBC at 1.0 µg/mL). AMCP suppressed key inflammatory mediators (IL-6, IL-8, IL-1β, TNF-α, and PGE₂) in a concentration-dependent manner in both HaCaT keratinocytes and SZ95 sebocytes. Additionally, it promoted keratinocyte migration, upregulated the expression of epidermal differentiation genes (FLG, IVL, Claudin-1, and KRT1), and downregulated KLK7 expression. Notably, the combination of 2% propylene glycol and 0.1% sodium surfactin synergistically enhanced topical dermal delivery of AMCP, resulting in a 5-fold increase in cumulative permeation at 8 h. In conclusion, AMCP exerts anti-acne effects through a multi-functional mechanism involving sebum control, antibacterial activity, anti-inflammation, and cell migration, while also overcoming the bottleneck of topical dermal delivery. These findings provide a new cyclic peptide with anti-acne efficacy, positioning AMCP as a promisingly anti-acne ingredient.