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/ [email protected] ) stimuli-responsive microneedles (MNs) were designed for painless glucose-mediated transdermal administration. In this work, GOx and Co 2+ 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 H 2 O 2 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 Co 2+ ions in the MOF, the byproduct H 2 O 2 was decomposed. Possible free Co 2+ ions would be chelated by EDTA–SiO 2 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 H 2 O 2 and Co 2+ 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.