Glucose-responsive microneedle patch for closed-loop dual-hormone delivery in mice and pigs

Abstract

Insulin and glucagon secreted from the pancreas with dynamic balance play a vital role in regulating blood glucose levels. Although distinct glucose-responsive insulin delivery systems have been developed, the lack of a self-regulated glucagon release module limits their clinical applications due to the potential risk of hypoglycemia. Here, we describe a transdermal polymeric microneedle patch for glucose-responsive closed-loop insulin and glucagon delivery to achieve glycemic regulation with minimized risk of hypoglycemia. The glucose-responsive phenylboronic acid units can bind to glucose to reversibly shift the net charge (from positive to negative) of the entire polymeric matrix within microneedles. Therefore, the release ratio of the negatively charged insulin and the positively charged glucagon analog from the patch can be dynamically tuned upon the fluctuation of blood glucose levels to realize glycemic homeostasis. In both chemically induced type 1 diabetic mouse and minipig models, this glucose-responsive dual-hormone microneedle patch demonstrated tight long-term regulation in blood glucose levels (>24 hours in minipigs).

Human-Hair-Derived Natural Particles as Multifunctional Sunscreen for Effective UV Protection

“…Therefore, we further evaluated the ex vivo skin penetration of particles through topical application of them on pig skin (Figure 4A), as it could perfectly mimic the structure and function of human skin. 38,39 In order to directly observe the skin penetration, three types of particles, including TiO 2 , PDA, and HDPs, were labeled with Rhodamine B isothiocyanate (RBITC), and the free RBITC was set as the control to simulate the free organic UV filter. Fluorescence imaging was employed to investigate the penetration of particles in each group after the pig skin was incubated with particles.…”

Highlights from the Diabetes UK Professional Conference 2023

“…Insulin is negatively charged, and glucagon positive, Prof Heise explained, so electrostatic interactions from glucose shifts can be used to release each hormone in response to glucose levels. In minipigs, this controlled blood glucose with less hypoglycaemia than subcutaneous insulin 5 . Although Prof Heise noted that some hypoglycaemia still occurred, ‘it will be very hard to obliterate hypos’.…”

“…In minipigs, this controlled blood glucose with less hypoglycaemia than subcutaneous insulin. 5 Although Prof Heise noted that some hypoglycaemia still occurred, 'it will be very hard to obliterate hypos'.…”

Microneedle-Mediated Transdermal Delivery of Biopharmaceuticals

“…The release of insulin and glucagon could be adjusted automatically by the change in the blood glucose levels. The researchers demonstrated the long-term effectiveness of this microneedle system on mice and minipigs with induced type 1 diabetes [ 197 ]. Demir et al employed the combination of gelatin methacrylate, polyethylene glycol diacrylate, and MoS2 nanosheets to fabricate polymeric microneedles with desired drug release kinetics.…”