期刊
NANO RESEARCH
卷 14, 期 8, 页码 2689-2696出版社
TSINGHUA UNIV PRESS
DOI: 10.1007/s12274-020-3273-z
关键词
drug delivery; diabetes; glucose-responsive; pH-sensitive; microneedle
类别
资金
- National Key R&D Program of China [2017YFA0205600]
- National Natural Science Foundation of China [31771091, 51922043]
- Guangdong Natural Science Funds for Distinguished Young Scholar [2017A030306018]
- Guangdong Provincial Programs [2017ZT07S054, 2017GC010304]
- Outstanding Scholar Program of Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) [2018GZR110102001]
- Guangdong Natural Science Foundation [2018A030310285]
- Science and Technology Program of Guangzhou [201902020018, 201804020060, 201904010398]
- Fundamental Research Funds for Central Universities
- National Science Foundation [1919285]
- American Diabetes Association [1-15-ACE-21]
- Direct For Mathematical & Physical Scien [1919285] Funding Source: National Science Foundation
- Division Of Materials Research [1919285] Funding Source: National Science Foundation
The study presents a novel glucose-responsive insulin delivery system using pH-sensitive insulin-loaded nanoparticles and glucose oxidase-catalase-loaded pH-insensitive nanoparticles. This system effectively regulates blood glucose levels within normal ranges for a prolonged period and reduces inflammation risks towards normal skin.
Glucose-responsive insulin delivery systems show great promise to improve therapeutic outcomes and quality of life for people with diabetes. Herein, a new microneedle-array patch containing pH-sensitive insulin-loaded nanoparticles (NPs) (SNP(I)) together with glucose oxidase (GOx)- and catalase (CAT)-loaded pH-insensitive NPs (iSNP(G+C)) is constructed for transcutaneous glucose-responsive insulin delivery. SNP(I) are prepared via double emulsion from a pH-sensitive amphiphilic block copolymer, and undergo rapid dissociation to promote insulin release at a mild acidic environment induced by GOx in iSNP(G+C) under hyperglycemic conditions. CAT in iSNP(G+C) can further consume excess H2O2 generated during GOx oxidation, and thus reduce the risk of inflammation toward the normal skin. The in vivo study on type 1 diabetic mice demonstrates that the platform can effectively regulate blood glucose levels within normal ranges for a prolonged period.
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