期刊
BIOMATERIALS
卷 267, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.120458
关键词
Glucose-responsive; Drug delivery; Microgels; Nanoparticles; Insulin; Diabetes
资金
- Helmsley Charitable Trust
- Koch Institute Support (core) Grant from the National Cancer Institute at the NIH [P30-CA14051]
- NSF Graduate Research Fellowships
A glucose-responsive insulin delivery system was developed using encapsulated nanoparticles and microgels, showing extended glycemic control in diabetic mice and a similar response to glucose challenge compared to healthy animals in animal studies.
An insulin delivery system that self-regulates blood glucose levels has the potential to limit hypoglycemic events and improve glycemic control. Glucose-responsive insulin delivery systems have been developed by coupling glucose oxidase with a stimuli-responsive biomaterial. However, the challenge of achieving desirable release kinetics (i.e., insulin release within minutes after glucose elevation and duration of release on the order of weeks) still remains. Here, we develop a glucose-responsive delivery system using encapsulated glucose-responsive, acetalated-dextran nanoparticles in porous alginate microgels. The nanoparticles respond rapidly to changes in glucose concentrations while the microgels provide them with protection and stability, allowing for extended glucose-responsive insulin release. This system reduces blood sugar in a diabetic mouse model at a rate similar to naked insulin and responds to a glucose challenge 3 days after administration similarly to a healthy animal. With 2 doses of microgels containing 60 IU/kg insulin each, we are able to achieve extended glycemic control in diabetic mice for 22 days.
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