Isoliquiritigenin micellar microneedle for pH monitoring and diabetic wound healing
Huaqian Xue, Chen Zhang, Dini Lin, Qiancheng Gu, Chuchu Sun, Xiufei Lin, Chi Zhang, Lanjie Lei, Liangle Liu
Abstract
Chronic inflammation, oxidative stress, and insufficient angiogenesis hinder wound healing in patients with diabetes, necessitating long-term management strategies. In this study, we developed pH-responsive hydrogel microneedles (LSI-GCA) based on Lycium barbarum polysaccharide stearate micelles that could achieve real-time pH monitoring and intelligent drug release for effective wound management. LSI-GCA was prepared through hydrophobic modification and isoliquiritigenin (ISO) loading, followed by its combination with a chitosan/anthocyanin backing layer. LSI-GCA exhibited excellent biocompatibility and antibacterial and antioxidant properties by activating the NRF2 pathway and inhibiting pro-inflammatory factors. Animal experiments confirmed that LSI-GCA significantly accelerated wound healing in a diabetic model and promoted angiogenesis, collagen deposition, and M2 macrophage polarization. Genomic and network pharmacological analyses revealed a multi-target synergistic mechanism involving the modulation of EGFR/VEGF signaling to promote proliferation, inhibition of inflammatory pathway (NF-κB), and repair of DNA damage through upregulation of BRCA1/2. This study provides an integrated "monitoring-treatment" strategy for diabetic wounds, offering great potential for clinical transformation and personalized treatment.