Core-Shell Microneedle Gel for Self-Regulated Insulin Delivery

被引:290
作者
Wang, Jinqiang [1 ,2 ,3 ,4 ]
Ye, Yanqi [1 ,2 ,3 ,4 ]
Yu, Jicheng [1 ,2 ,3 ,4 ]
Kahkoska, Anna R. [5 ]
Zhang, Xudong [1 ,2 ,3 ,4 ]
Wang, Chao [1 ,2 ,3 ,4 ]
Sun, Wujin [1 ,2 ,3 ,4 ]
Corder, Ria D. [6 ]
Chen, Zhaowei [1 ,2 ,3 ,4 ]
Khan, Saad A. [6 ]
Buse, John B. [5 ]
Gu, Zhen [1 ,2 ,3 ,4 ,5 ]
机构
[1] Univ North Carolina Chapel Hill, Joint Dept Biomed Engn, Raleigh, NC 27695 USA
[2] North Carolina State Univ, Raleigh, NC 27695 USA
[3] Univ North Carolina Chapel Hill, Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27599 USA
[4] Univ North Carolina Chapel Hill, Eshelman Sch Pharm, Ctr Nanotechnol Drug Delivery, Chapel Hill, NC 27599 USA
[5] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA
[6] North Carolina State Univ, Dept Chem & Biomol Engn, Raleigh, NC 27695 USA
基金
美国国家科学基金会;
关键词
microneedle; stimuli-responsive; diabetes; drug delivery; hydrogel; GLUCOSE-RESPONSIVE INSULIN; CATIONIC COPOLYMER HYDROGELS; TRANSCUTANEOUS PATCHES; PHYSIOLOGICAL PH; SENSING MOIETY; DRUG-DELIVERY; IN-VIVO; ACID; RELEASE; SKIN;
D O I
10.1021/acsnano.7b08152
中图分类号
O6 [化学];
学科分类号
070301 [无机化学];
摘要
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.
引用
收藏
页码:2466 / 2473
页数:8
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