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Glucose-responsive insulin patch for the regulation of blood glucose in mice and minipigs
Name
nihms-1578301.pdf
Description
Accepted version
Size
1.39 MB
Format
Adobe PDF
Checksum (MD5)
0d5f1343b29cd381642253a5f5eb696d
Author(s)
Yu, Jicheng
Wang, Jinqiang
Zhang, Yuqi
Chen, Guojun
Mao, Weiwei
Ye, Yanqi
Kahkoska, Anna R
Buse, John B
Langer, Robert
Gu, Zhen
Date Issued
2020
Journal
Nature Biomedical Engineering
Publisher
Springer Science and Business Media LLC
Version
Author's final manuscript
Abstract
© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Glucose-responsive insulin delivery systems that mimic pancreatic endocrine function could enhance health and improve quality of life for people with type 1 and type 2 diabetes with reduced β-cell function. However, insulin delivery systems with rapid in vivo glucose-responsive behaviour typically have limited insulin-loading capacities and cannot be manufactured easily. Here, we show that a single removable transdermal patch, bearing microneedles loaded with insulin and a non-degradable glucose-responsive polymeric matrix, and fabricated via in situ photopolymerization, regulated blood glucose in insulin-deficient diabetic mice and minipigs (for minipigs >25 kg, glucose regulation lasted >20 h with patches of ~5 cm2). Under hyperglycaemic conditions, phenylboronic acid units within the polymeric matrix reversibly form glucose–boronate complexes that—owing to their increased negative charge—induce the swelling of the polymeric matrix and weaken the electrostatic interactions between the negatively charged insulin and polymers, promoting the rapid release of insulin. This proof-of-concept demonstration may aid the development of other translational stimuli-responsive microneedle patches for drug delivery.
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
10.1038/S41551-019-0508-Y
