Development and evaluation of a multifunctional natural composite microemulsion for anti-acne therapy: synergistic anti-inflammatory and antibacterial effects.

INTRODUCTION: Acne is a common inflammatory disease of the hair follicles and sebaceous glands, but most of the current treatments have side effects or drug resistance problems. This study developed a stable, self-emulsifying composite Microemulsion (PHS-ME) co-loaded with paeonol, honokiol and Salix alba (white willow) bark extract.

METHODS: The formulation was optimized using Box-Behnken design. Physicochemical properties, centrifugation and storage stability (35 days at 4 °C, 25 °C, and 40 °C), in vitro drug release, cytotoxicity (HaCaT cells), cellular uptake, anti-inflammatory activity (LPS-stimulated RAW264.7 cells), and antibacterial efficacy against Cutibacterium acnes and Staphylococcus aureus were evaluated.

RESULTS: PHS-ME exhibited a uniform spherical morphology with a mean droplet size of 13.54 ± 0.35 nm, high encapsulation efficiency, and excellent physical stability. It showed sustained drug release, good biocompatibility (safe up to 8 µg/mL). Finally, PHS-ME significantly enhanced the cellular uptake of HaCaT and effectively inhibited the production of key inflammatory mediators in RAW264.7. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of the composite Microemulsion against Cutibacterium acnes and Staphylococcus aureus for acne were the same, which were 0.5 mg/mL and 2 mg/mL respectively.

DISCUSSION: This study proposes a simple and stable strategy for preparing composite Microemulsion. Due to its synergistic anti-inflammatory and antibacterial properties, these Microemulsions have great industrial potential as a natural local anti-acne product.