Abstract：
: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.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Volpatti LR,Facklam AL,Cortinas AB,Lu YC,Matranga MA,MacIsaac C,Hill MC,Langer R,Anderson DGdoi
10.1016/j.biomaterials.2020.120458subject
Has Abstractpub_date
2021-01-01 00:00:00pages
120458eissn
0142-9612issn
1878-5905pii
S0142-9612(20)30704-3journal_volume
267pub_type
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