Charge-switchable polymeric complex for glucose-responsive insulin delivery in mice and pigs.

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 Adv

journal_title

Science advances

authors

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 Z

doi

10.1126/sciadv.aaw4357

subject

Has Abstract

pub_date

2019-07-10 00:00:00

pages

eaaw4357

issue

7

issn

2375-2548

pii

aaw4357

journal_volume

5

pub_type

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