Cited by 604Advancements in Transdermal Drug DeliveryDiabetes Management and ResearchPancreatic function and diabetes

Glucose-responsive insulin patch for the regulation of blood glucose in mice and minipigs

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Yu, Jicheng, Wang, Jinqiang, Zhang, Yuqi, Chen, Guojun, Mao, Weiwei, Ye, Yanqi, Kahkoska, Anna R., Buse, John B. +2 more·2020·Nature Biomedical Engineering

Abstract

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 cm 2). 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.

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  • Another study used phenylboronic acid units and ISF glucose to trigger insulin release based on weakening of electrostatic interactions between insulin and microneedle matrix in a mice model.

    “Similarly, another research study [165] used phenylboronic acid units and ISF glucose to trigger the insulin release based on the weakening of the electrostatic interactions between the insulin and microneedle matrix in a mice model.”

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Authors
Yu, J., Wang, J., Zhang, Y., Chen, G., Mao, W., Ye, Y., Kahkoska, A. R., Buse, J. B., Langer, R., & Gu, Z.
Affiliations
University of North Carolina at Chapel Hill (US)
Corresponding author
Gu, Zhen
Venue
Nature Biomedical Engineering
Published
2020-02-03
Volume
4
Issue
5
Pages
499-506
ISSN
2157-846X (ISSN-L)
OpenAlex
W3004097028
Cited by
604
References
50
Citations by year
2026: 54 · 2025: 106 · 2024: 102 · 2023: 100 · 2022: 109 · 2021: 83 · 2020: 50
FWCI
33.35
Type
journal article
Language
en
Open access
Locations
  • Nature Biomedical Engineering (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
UC | University of California, Los Angeles
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
glucose-responsive insulin delivery, transdermal patch, microneedles, phenylboronic acid, stimuli-responsive polymers, in situ photopolymerization, blood glucose regulation, diabetes mellitus, insulin secretion, insulin-deficient diabetes, minipigs
MeSH terms
Insulin Secretion, Animals, Blood Glucose, Diabetes Mellitus, Experimental, Disease Models, Animal, Humans, Insulin, Male, Mice, Inbred C57BL, Needles, Swine, Swine, Miniature, Drug Delivery Systems, Transdermal Patch

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