A novel cell-penetrating peptide supports hair follicle growth through anti-inflammatory and growth factor-associated mechanisms in preclinical models

Abstract

Background Hair loss remains a prevalent condition for both men and women worldwide. Current therapies for this condition, including minoxidil and finasteride, are limited by inconsistent efficacy, side effects, and dependence on continuous use. Cell-penetrating peptides (CPPs) have emerged as promising bioactive agents in dermatology due to their ability to traverse cell membranes and modulate multiple biological pathways relevant to hair regeneration. Objective This study aimed to identify and evaluate a novel synthetic CPP, DualPep-ALO, for its potential to promote hair growth by restoring the follicular microenvironment and stimulating key regenerative pathways. Methods Using the intra-dermal delivery technology platform (REMEDI), over 200 human protein-derived peptides were screened for cell-penetrating potential. The lead candidate, DualPep-ALO, was selected based on its proliferative effect on human follicle dermal papilla cells and upregulation of Wnt/beta-catenin and ERK signaling. In vitro and ex vivo assays were conducted to assess antioxidant enzyme activity, inflammatory cytokine suppression, follicle elongation, anagen maintenance, and growth factor expression. Results DualPep-ALO significantly enhanced human follicle dermal papilla cell proliferation, restored antioxidant enzyme (SOD, CAT) activity, and suppressed pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6, PGE-2). In ex vivo human scalp tissue, it promoted hair follicle elongation, maintained the anagen phase, and upregulated VEGF, HGF, and EGF expression, achieving outcomes comparable to minoxidil. Conclusion DualPep-ALO demonstrates potent antioxidant, anti-inflammatory, and pro-regenerative effects, restoring follicular vitality through multimodal biological pathways. These findings support its potential as a novel CPP-based topical agent for hair loss, warranting further clinical investigation to validate efficacy, safety, and long-term therapeutic potential.