PVA-based bulk microneedles capable of high insulin loading and pH-triggered degradation for multi-responsive and sustained hypoglycemic therapy

"Closed-loop" insulin-loaded microneedle patche shows great promise for improving therapeutic outcomes and life quality for diabetes patients. However, it is typically hampered by limited insulin loading capacity, random degradation, and intricate preparation procedures for the independenc...

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Bibliographic Details
Published in:Biomaterials science 2024-01, Vol.12 (2), p.57-517
Main Authors: Ma, Yuhong, Wang, Wei, He, Mujiao, Liu, Yunzhu, Li, Caihua, Zhong, Yinan, Bu, Quanmin, Huang, Dechun, Qian, Hongliang, Chen, Wei
Format: Article
Language:English
Subjects:
Animals
Closed loops
Degradation
Diabetes
Diabetes Mellitus, Experimental - drug therapy
Drug Delivery Systems - methods
Gluconic acid
Glucose
Glucose - metabolism
Humans
Hydrogen-Ion Concentration
Hypoglycemic Agents - therapeutic use
Insulin
Insulin - chemistry
Needles
Oxidation
Photopolymerization
Polyvinyl alcohol
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Summary:"Closed-loop" insulin-loaded microneedle patche shows great promise for improving therapeutic outcomes and life quality for diabetes patients. However, it is typically hampered by limited insulin loading capacity, random degradation, and intricate preparation procedures for the independence of the "closed-loop" bulk microneedles. In this study, we combined the solubility of microneedles and "closed-loop" systems and designed poly(vinyl alcohol)-based bulk microneedles (MNs@GI) through in situ photopolymerization for multi-responsive and sustained hypoglycemic therapy, which significantly simplified the preparation process and improved insulin loading. GOx/insulin co-encapsulated MNs@GI with a phenylboronic ester structure improved glycemic responsiveness to control the insulin release under high glucose conditions and reduced inflammation risk in the normal skin. MNs@GI could further degrade to increase insulin release due to the crosslinked acetal-linkage hydrolysis in the presence of gluconic acid, which was caused by GOx-mediated glucose-oxidation in a hyperglycemic environment. The in vivo results showed that MNs@GI effectively regulated glycemic levels within the normal range for approximately 10 h compared to that of only insulin-loaded microneedles (MNs@INS). Consequently, the highly insulin-loaded, multi-responsive, and pH-triggered MN system has tremendous potential for diabetes treatment. "Closed-loop" insulin-loaded microneedle patches show great promise for improving therapeutic outcomes and life quality for diabetes patients.
ISSN:2047-4830
2047-4849
DOI:10.1039/d3bm01760e