Figure 4.

Schematic of glucose-responsive insulin delivery microneedles: (a) A dual-module microneedle patch to separately encapsulate insulin and glucagon. The two modules comprise different ratios of key monomers, synergistically responding to both hyperglycemic and hypoglycemic states (reproduced with permission from Wang et al., Proceedings of the National Academy of Sciences of the United States of America; published by National Academy of Sciences, 2020) [174]; (b) fast-responsive MN patch loaded with hypoxia-sensitive hyaluronic acid (HS-HA) vesicles containing insulin and GOx. In localized hypoxic environment, the hydrophobic 2-nitroimidazole groups of HS-HA are reduced to hydrophilic 2-aminoimdazole, leading to the dissociation of vesicles and subsequent release of insulin (reproduced with permission from Yu et al., Proceedings of the National Academy of Sciences of the United States of America; published by National Academy of Sciences, 2015) [179]; (c) the insulin and glucose oxidase are encapsulated in metal–organic framework and further loaded into the microneedle matrix. The low pH induced by glucose oxidation leads to framework degradation and insulin release. The preloaded Co²⁺ catalyzes the decomposition of the byproduct H₂O₂. The excessive Co²⁺ is chelated by EDTA-SiO₂ nanoparticles in the microneedle matrix (reproduced with permission from Yang et al., ACS Applied Materials & Interfaces; published by ACS, 2020) [176].