From Bioactive Peptides to Transdermal Peptides: An Emerging Strategy for Revolutionizing Drug Delivery

Transdermal peptides, Engineered from bioactive peptides through rational sequence modification and structural optimization, transdermal peptides have emerged as a transformative strategy for enhancing the transdermal delivery of macromolecular drugs, proteins, and nucleic acids. This review outlines the structural classifications of bioactive peptides, including short, linear, cyclic, cationic, anionic, and neutral peptides, as well as their diverse biological sources. It focuses on the design principles and penetration mechanisms of transdermal peptides. These peptides interact dynamically with skin constituents, such as lipids and keratins, by fine-tuning the hydrophilic-hydrophobic balance, molecular weight, and conformational stability. This transiently disrupts the stratum corneum barrier and facilitates drug permeation via endocytosis and receptor-mediated pathways. They find applications in various pharmaceutical domains, including localized anticancer and antimicrobial therapies, as well as in cosmetics for whitening, anti-aging, and moisturizing. They are also being explored in innovative areas such as hair regeneration and wound healing. When combined with advanced delivery platforms, such as nanocarriers, microneedles, and microfluidic systems, transdermal peptides can significantly improve targeting efficacy and enable controlled release. Despite challenges related to peptide immunogenicity and scalable synthesis, the future integration of smart, stimuli-responsive technologies and artificial intelligence promises to Bioactive peptides, Skin permeation mechanisms, Skin transmission, Transdermal peptidesadvance personalized transdermal therapeutics.