自己修復型PVA/PVPミセル-ヒドロゲル複合システムを用いたてんかん薬フェニトインの創傷治癒への応用

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.