Self-healing PVA/PVP micelle-hydrogel composite system for potential phenytoin repositioning in wound healing

The treatment of chronic and infected wounds remains a constant challenge; therefore, there is a need to develop multifunctional dressings that integrate mechanical resilience and antimicrobial activity via alternative drugs to prevent bacterial resistance. This study presents, for the first time, the design of self-healing hydrogels based on polyvinyl alcohol and polyvinylpyrrolidone, which were obtained by the freeze‒thaw method; these hydrogels enable physical crosslink formation without the use of toxic agents and serve as carriers for phenytoin repositioning, an antiepileptic drug recognized for its wound-healing properties. Phenytoin was incorporated via micelle-assisted solubilization, ensuring uniform distribution without damaging the hydrogel structure. The optimal formulation exhibited high swelling capacity (~ 450%), gradual disintegration (55% in 14 days), pseudoplastic behavior, and excellent self-healing ability even after multiple deformation cycles. Structural analyses (FTIR, DSC, TGA, SEM) confirmed dynamic hydrogen bonding interactions and an interconnected porous network conducive to tissue regeneration. Phenytoin release followed a diffusion mechanism, with a rapid initial phase followed by sustained release driven by chain relaxation and erosion, reaching 55% release in 4 days. The inclusion of phenytoin imparted antimicrobial activity, with 52% inhibition against Staphylococcus aureus and 30% against Pseudomonas aeruginosa. The results position this system as a groundbreaking alternative for phenytoin repurposing in wound treatment.