Pyrogallol-rich supramolecular hydrogels with enzyme-sensitive microdomains for controlled topical delivery of hydrophobic drugs

Skin wound treatments require efficient and targeted delivery of therapeutic agents to promote fast tissue regeneration and prevent infections. Hydrogels are one of the most popular products in the wound care market, although their use as medicated wound dressings remains a massive challenge when hydrophobic drugs are needed due to the hydrophilic nature of these soft materials. In this study, we developed innovative, dynamic hydrogels based on polyvinyl alcohol (PVA), pyrogallol as a hydrogen bond crosslinker, and casein micelles as hydrophobic reservoirs of silver sulfadiazine (SSD) for enzyme-activated smart delivery at wound sites. The hydrogel formulation was optimized for mechanical strength, viscoelastic behavior, water absorption capacity, and drug-loading efficiency. In vitro drug delivery studies revealed a sustainable release profile of SSD for over 24 h from the micelles within the hydrogel network. Furthermore, biocompatibility evaluation using mouse fibroblast L929 cells demonstrated that the hydrogel did not inhibit cell viability, while in vivo experiments on Caenorhabditis elegans (C. elegans) proved its safety in complex organisms. This versatile hydrogel also has anti-inflammatory and antibacterial effects stemming from the therapeutic polyphenol, which could benefit the healing process. The combination of PVA, pyrogallol, and casein-based nanocarriers could offer an approach to wound healing, providing a new platform for hosting hydrophobic therapeutic substances. Overall, this hydrogel system shows great promise in wound care and could broaden the applications of this family of soft materials for treating various skin injuries.