Abstract:
:Glucose-responsive insulin delivery systems with robust responsiveness that has been validated in animal models, especially in large animal models, remain elusive. Here, we exploit a new strategy to form a micro-sized complex between a charge-switchable polymer with a glucose-sensing moiety and insulin driven by electrostatic interaction. Both high insulin loading efficiency (95%) and loading capacity (49%) can be achieved. In the presence of a hyperglycemic state, the glucose-responsive phenylboronic acid (PBA) binds glucose instantly and converts the charge of the polymeric moiety from positive to negative, thereby enabling the release of insulin from the complex. Adjusting the ratio of the positively charged group to PBA achieves inhibited insulin release from the complex under normoglycemic conditions and promoted release under hyperglycemic conditions. Through chemically induced type 1 diabetic mouse and swine models, in vivo hyperglycemia-triggered insulin release with fast response is demonstrated after the complex is administrated by either subcutaneous injection or transdermal microneedle array patch.
journal_name
Sci Advjournal_title
Science advancesauthors
Wang J,Yu J,Zhang Y,Zhang X,Kahkoska AR,Chen G,Wang Z,Sun W,Cai L,Chen Z,Qian C,Shen Q,Khademhosseini A,Buse JB,Gu Zdoi
10.1126/sciadv.aaw4357subject
Has Abstractpub_date
2019-07-10 00:00:00pages
eaaw4357issue
7issn
2375-2548pii
aaw4357journal_volume
5pub_type
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