Multi-targeted synergy of Bacillus sp. TC5 fermentation products for transdermal drug delivery and hair regeneration

INTRODUCTION: The stratum corneum represents a major barrier to transdermal drug delivery, while limited follicular activity contributes to hair loss disorders. Bacillus species, generally recognized as safe microorganisms, have broad applications in biotechnology and industry; however, their application in the cosmetics and pharmaceutical industries still faces certain challenges. OBJECTIVE: Bacillus sp. TC5 is a high-yield keratinase-producing strain. This study evaluated the dermatological potential of Bacillus sp. TC5 fermentation products, focusing on their dual functions in enhancing transdermal drug delivery and promoting hair growth through biochemical and molecular mechanisms. METHODS: Non-targeted metabolomics identified bioactive metabolites in TC5 fermentation products. Franz diffusion assays assessed their ability to enhance transdermal permeation of pharmaceuticals (5-fluorouracil, minoxidil, ketoprofen) and cosmetic agents (niacinamide, tripeptides, decapeptides). In vivo efficacy was examined in C57BL/6 mice through hair regrowth observation, follicle morphology (HE staining), and immunofluorescence staining for protein expression. RESULTS: TC5 fermentation products were non-toxic to HDFs, HaCaT cells (200-800 μg/mL), and DPCs (100-500 μg/mL) without inducing ROS. They markedly enhanced skin permeability, shortening lag time and increasing drug permeation. In vivo treatment improved follicle density and diameter, with increased ALP, K5, and Ki67 expression indicating dermal papilla activation. Mechanistically, the products stimulated the Wnt10b/β-catenin and VEGF/IGF-1 pathways, promoting follicular proliferation, angiogenesis, and epithelial renewal, while suppressing TGF-β1 and FGF5 and modulating BMP6 to prolong the anagen phase. Upregulation of keratin 14 and 17 strengthened hair shaft integrity. CONCLUSION: Bacillus sp. TC5 fermentation products effectively promote hair regrowth and enhance transdermal drug absorption. These findings highlight TC5 metabolites as promising, eco-friendly candidates for developing novel skin penetration enhancers and cosmeceuticals for hair restoration and skin repair.