Composition-Engineered Metal–Organic Framework-Based Microneedles for Glucose-Mediated Transdermal Insulin Delivery

Elaborately designed glucose-responsive insulin-delivery systems are highly desirable for the treatment of diabetes because it can secrete insulin depending on blood glucose levels. Herein, mimic multi-enzyme metal-organic framework (MOF)-based (insulin and glucose oxidase-loaded cobalt-doped ZIF-8, abbreviated as Ins/GOx@Co-ZIF-8) stimuli-responsive microneedles (MNs) were designed for painless glucose-mediated transdermal administration. In this work, GOx and Co2+ ions were engineered into MOFs to construct a mimic multi-enzyme vehicle. GOx in the MOF, as the glucose-responsive factor, could catalyze glucose into gluconic acid with the formation of H2O2 as the byproduct. The gluconic acid formed decreases the local pH in MOFs, resulting in the degradation of MOFs and thus preloaded insulin would be released. Meanwhile, catalyzed by Co2+ ions in the MOF, the byproduct H2O2 was decomposed. Possible free Co2+ ions would be chelated by EDTA-SiO2 nanoparticles in MNs and removed by peeling MNs off. The as-obtained mimic multi-enzyme MOF-based MNs showed good dependence on glucose concentration without divulging H2O2 and Co2+ ions and enough stiffness to penetrate into skin. This study offers a new strategy, using facilely synthesized MOFs as depots to integrate with MNs, for designing stimuli-responsive transdermal drug-delivery systems.