Elastin-derived peptide hydrogels for sustained dermal delivery of tetrapeptide-21

Tetrapeptide-21 (GEKG) has demonstrated anti-aging efficacy. This work emphasises the need for advanced delivery systems beyond conventional topicals and highlights elastin-derived peptides (EDPs) as promising hydrogel-forming carriers due to their self-assembly, crosslinking ability, and sustained bioactive peptide release. First- and second-generation EDPs were designed, synthesised and evaluated for their ability to encapsulate drug molecules. Using the collagen-stimulating tetrapeptide-21 (a bioactive peptide that promotes tissue repair), we assessed their encapsulation and permeation properties. Transmission electron microscopy (TEM) revealed uniform nanofibres with a hollow structure, suggesting their potential for molecular scaffolding and sustained drug delivery. Both peptide generations sustained skin permeation of tetrapeptide-21, achieving permeation rates of 7.5 % to 20.9 % over 72 h, compared to 26.6 % for the free drug solution. The second-generation exhibited superior matrix-forming ability, which led to slower skin permeation. This is attributable to the reduced positive charge in the second-generation hydrogels, which enhanced their physical robustness. Given their tuneable release profiles, these hydrogels hold potential not only for cosmetic applications but also for therapeutic uses.