Journal
ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 5, Issue 11, Pages 5781-5789Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.9b00532
Keywords
microneedle fabrication; semi-interpenetrating network hydrogel; glucose-responsive; insulin; phenylboronic acid; diabetes mellitus
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Funding
- Kanagawa Institute of Industrial Science and Technology (KISTEC)
- Cooperative Research Project of Research Center for Biomedical Engineering
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
- Program for Building Regional Innovation Ecosystems (MEXT)
- Japan Science and Technology Agency (Start-ups from Advanced Research and Technology program)
- Japan Agency for Medical Research and Development (Acceleration Transformative Research for Medical Innovation program)
- Secom Science and Technology Foundation
- Japan Science and Technology Agency (Center of Innovation Stream)
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Microneedle (MN) technology, which can transdermally deliver insulin in a noninvasive manner, offers a promising way to replace subcutaneous self-injection for diabetes management. Hydrogel is an attractive candidate for MN fabrication because of its biocompatibility, controllable degradability, and possibility to achieve sustained as well as stimuli-responsive drug delivery. Herein, we report a smart MN composed of a semi-interpenetrating network (semi-IPN) hydrogel prepared by biocompatible silk fibroin (SF) and phenylboronic acid/acrylamide for glucose-responsive insulin delivery. Six fabrication methods were investigated to maintain the glucose sensitivity of the hydrogel while avoiding deformation during fabrication. The optimized method was to fabricate smart MNs using a two-layer strategy, with a needle region formed by the SF combined semi-IPN hydrogel and the base layer fabricated by SF. The hybrid MN autonomously released insulin well-correspondent to the glucose change pattern via the regulation of the skin layer formed on the surface. Furthermore, this hybrid MN retained its original needle shape after 1 week in aqueous system, thus eliminating the safety concerns associated with dissolving MNs and suggesting the possibility for sustained delivery. This nondegradable smart MN is promising to provide on-demand insulin in a long-acting, painless, and convenient way.
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