A multimodal therapy for infected diabetic wounds based on glucose-responsive nanocomposite-integrated microneedles.

Diabetic wounds in a state of high glucose are refractory to treatment and healing, especially if they are infected with bacteria. Herein, a novel nanocomposite (CIP/GOx@ZIF-8) was synthesized by loading ciprofloxacin hydrochloride (CIP) and glucose oxidase (GOx) into zeolitic imidazole framework-8 (ZIF-8) that exhibited good glucose sensitivity and catalytic activity. The high glucose in diabetic wounds could be decomposed into hydrogen peroxide (HO) and gluconic acid the catalysis of GOx, which further destroyed CIP/GOx@ZIF-8 to release Zn and cargos. The combination of glucose starvation, Zn, HO and CIP could elevate the antibacterial effect and reduce bacterial resistance. Subsequently, the nanocomposite was fabricated into dissolving microneedles (CIP/GOx@ZIF-8 MNs) using polyvinylpyrrolidone (PVP). The microneedles exhibited good mechanical strength, puncture performance, dissolving performance, glucose responsiveness, antibacterial performance and biocompatibility. For wound healing, CIP/GOx@ZIF-8 MNs with good biosafety facilitated neovascularization and collagen deposition as well as reduced inflammation, and the wounds were almost healed after treatment. This multimodal therapeutic strategy is created to provide a unique treatment for infected diabetic wounds.