JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE A

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Preparation and properties of poly(ethylene glycol)-b- poly(3-acrylamidophenylboronic acid) glucose responsive particles and their hyaluronic acid-based microneedle patches

Author(s): Yichuan HONG, Haojie YU, Li WANG, Xiang CHEN, Di SHEN, Yu WANG, Shuning REN, Yudi HUANG, Jian YANG
Affiliation(s): State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China; more
Corresponding email(s): hjyu@zju.edu.cn
Key Words: Diabetes; Hyaluronic acid; Phenylboronic acid (PBA); Glucose responsive hydrogel; Microneedles

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Yichuan HONG, Haojie YU, Li WANG, Xiang CHEN, Di SHEN, Yu WANG, Shuning REN, Yudi HUANG, Jian YANG. Preparation and properties of poly(ethylene glycol)-b- poly(3-acrylamidophenylboronic acid) glucose responsive particles and their hyaluronic acid-based microneedle patches[J]. Journal of Zhejiang University Science A,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.A2300386

@article{title="Preparation and properties of poly(ethylene glycol)-b- poly(3-acrylamidophenylboronic acid) glucose responsive particles and their hyaluronic acid-based microneedle patches",
author="Yichuan HONG, Haojie YU, Li WANG, Xiang CHEN, Di SHEN, Yu WANG, Shuning REN, Yudi HUANG, Jian YANG",
journal="Journal of Zhejiang University Science A",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.A2300386"
}

%0 Journal Article
%T Preparation and properties of poly(ethylene glycol)-b- poly(3-acrylamidophenylboronic acid) glucose responsive particles and their hyaluronic acid-based microneedle patches
%A Yichuan HONG
%A Haojie YU
%A Li WANG
%A Xiang CHEN
%A Di SHEN
%A Yu WANG
%A Shuning REN
%A Yudi HUANG
%A Jian YANG
%J Journal of Zhejiang University SCIENCE A
%P 395-410
%@ 1673-565X
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.A2300386"

TY - JOUR
T1 - Preparation and properties of poly(ethylene glycol)-b- poly(3-acrylamidophenylboronic acid) glucose responsive particles and their hyaluronic acid-based microneedle patches
A1 - Yichuan HONG
A1 - Haojie YU
A1 - Li WANG
A1 - Xiang CHEN
A1 - Di SHEN
A1 - Yu WANG
A1 - Shuning REN
A1 - Yudi HUANG
A1 - Jian YANG
J0 - Journal of Zhejiang University Science A
SP - 395
EP - 410
%@ 1673-565X
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.A2300386"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: To overcome the pain and risk of hypoglycemia in insulin administration, glucose-responsive microneedles have been developed by researchers, which could release insulin according to the blood glucose level. We designed a kind of particles by a reversible addition-fragmentation chain transfer (RAFT) method containing a phenylboronic acid group as the sensor of glucose and carrier of insulin. poly(ethylene glycol) (PEG)‍-2-‍(dodecylthio(thiocarbonyl)thio)‍-2-methylpropionic acid (DDMAT) was synthesized as a macromolecular RAFT agent, which was then reacted with 3-acrylamidophenylboronic acid (AAPBA) to synthesize the block copolymer PEG-b-PAAPBA. Glucose-responsive particles loaded with insulin were prepared by self-assembly based on hydrophilic-hydrophobic interactions. Microneedle patches loaded with glucose-responsive particles were prepared using hyaluronic acid as the substrate. The insulin release behavior of the particles in glucose solutions of 0, 100, and 400 mg/dL showed significant glucose responsiveness and good biosafety. The results of blood glucose control experiments in rats indicate that a single microneedle patch can effectively maintain normal blood glucose for over 7 h.

聚乙二醇-b-聚丙烯酰胺基苯硼酸葡萄糖响应粒子及其透明质酸微针贴片的制备与性能研究

作者：洪溢川¹，俞豪杰^1,2，王立^1,2，陈翔¹，沈迪¹，任书宁¹，黄宇笛¹，杨健¹
机构：¹浙江大学，化学工程与生物工程学院，化学工程联合国家重点实验室，中国杭州，310058；²浙江-俄罗斯光电磁功能材料联合实验室，中国杭州，310058
目的：微针给药具有高效、方便、无痛等特点，有望用于透皮递送胰岛素治疗糖尿病。本文旨在制备糖敏响应负载胰岛素粒子，然后与透明质酸混合制备糖敏微针贴，研究其糖敏响应性能和对糖尿病大鼠的血糖控制性能。
创新点：1.通过嵌段共聚物的亲疏水自组装制备葡萄糖响应粒子并负载了胰岛素；2.制备苯硼酸基糖敏微针贴，此微针贴具有较好的血糖控制性能。
方法：1.通过可逆加成-断裂链转移聚合（RAFT）反应制备不同链长的PEG-b-PAAPBA嵌段共聚物（图4）；2.通过嵌段共聚物在不同pH值下的亲疏水相互作用，自组装制备葡萄糖响应粒子NP-PEG₁₁₄-b-PAAPBA_n，并负载胰岛素（图7）；3.用NP-PEG₁₁₄-b-PAAPBA_n负载胰岛素粒子和透明质酸制备糖敏微针贴，并通过动物实验验证所得糖敏微针贴片具有较好的血糖控制性能（图15和21）。
结论：1.合成了不同链长的PEG-b-PAAPBA嵌段共聚物，并通过自组装方法制备了葡萄糖响应粒子NP-PEG₁₁₄-b-PAAPBA_n并负载了胰岛素；2.用NP-PEG₁₁₄-b-PAAPBA_n负载胰岛素粒子和透明质酸制备了糖敏微针贴；3.所得糖敏微针贴片可以将糖尿病大鼠的血糖控制在正常水平超7h。

关键词组：糖尿病；透明质酸；苯硼酸；糖敏水凝胶；微针

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Reference

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聚乙二醇-b-聚丙烯酰胺基苯硼酸葡萄糖响应粒子及其透明质酸微针贴片的制备与性能研究

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