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/β-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-α, IL-1β, 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.