4.8 Article

Core-Shell Microneedle Gel for Self-Regulated Insulin Delivery

Journal

ACS NANO
Volume 12, Issue 3, Pages 2466-2473

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsnano.7b08152

Keywords

microneedle; stimuli-responsive; diabetes; drug delivery; hydrogel

Funding

  1. American Diabetes Association [1-15-ACE-21]
  2. National Science Foundation [1708620, 1542015]
  3. Alfred P. Sloan Foundation (Sloan Research Fellowship)
  4. NC TraCS
  5. NIH's Clinical and Translational Science Award (CTSA) [1UL1TR001111]
  6. State of North Carolina
  7. NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001111] Funding Source: NIH RePORTER
  8. NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [F30DK113728] Funding Source: NIH RePORTER

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A bioinspired glucose-responsive insulin delivery system for self regulation of blood glucose levels is desirable for improving health and quality of life outcomes for patients with type 1 and advanced type 2 diabetes. Here we describe a painless core-shell microneedle array patch consisting of degradable cross-linked gel for smart insulin delivery with rapid responsiveness and excellent biocompatibility. This gel-based device can partially dissociate and subsequently release insulin when triggered by hydrogen peroxide (H2O2) generated during the oxidation of glucose by a glucose-specific enzyme covalently attached inside the gel. Importantly, the H2O2-responsive microneedles are coated with a thin-layer embedding H2O2-scavenging enzyme, thus mimicking the complementary function of enzymes in peroxisomes to protect normal tissues from injury caused by oxidative stress. Utilizing a chemically induced type 1 diabetic mouse model, we demonstrated that this smart insulin patch with a bioresponsive core and protective shell could effectively regulate the blood glucose levels within a normal range with improved biocompatibility.

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