Glucose and pH Dual-Responsive Polymersomes with Multilevel Self-Regulation of Blood Glucose for Insulin Delivery,Biomacromolecules

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Glucose and pH Dual-Responsive Polymersomes with Multilevel Self-Regulation of Blood Glucose for Insulin Delivery
Biomacromolecules ( IF 5.5 ) Pub Date : 2021-08-23 , DOI: 10.1021/acs.biomac.1c00772
Dongxu Zhou ₁ , Siyu Li ₁ , Zhixiong Fei ₁ , Peng Zhou ₁ , Yaqi Zhao ₁ , Lunhao Zhi ₁ , Chenxi Li ₁ , Xu Peng ₂ , Xiaoling Liu ₁ , Changsheng Zhao _{1,

3}

Affiliation

Smart insulin delivery systems now play essential roles in diabetes treatment, whereas most existing systems suffer from insufficient regulation against blood glucose. Here, a glucose and pH dual-responsive insulin delivery system with multilevel self-regulation of blood glucose was constructed. Photocross-linked dual-responsive polymersomes were prepared by the self-assembly of the diblock copolymer methoxyl poly(ethylene glycol)-b-poly[3-acrylamidophenylboronic acid-co-2-(diethylamino)ethyl methacrylate-co-2-hydroxy-4-(methacryloyloxy)benzophenone] (mPEG-b-P(AAPBA-co-DEAEMA-co-BMA)) synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT), where insulin and glucose oxidase (GOx) were co-encapsulated inside. It is worth noting that the polymersomes with tunable membrane permeability are the first glucose-responsive platform consisting of both PBA and GOx. According to the pH change produced by gluconic acid, the pH-sensitive monomer DEAEMA endowed the polymersome membrane with multilevelly tunable and self-regulative permeability, further controlling the release behavior of insulin. This multilevel tunability was reflected directly in in vitro insulin release tests and was proven by the self-regulation of blood glucose in vivo. Promisingly, the polymersomes have great potential to be applied for the self-regulation of blood glucose in the treatment of diabetes.

中文翻译：

用于胰岛素输送的具有多级血糖自我调节的葡萄糖和 pH 双响应聚合物体

智能胰岛素输送系统现在在糖尿病治疗中发挥着重要作用，而大多数现有系统对血糖的调节不足。在这里，构建了具有多级血糖自我调节的葡萄糖和pH双响应胰岛素递送系统。-光致交联的双响应聚合物囊泡是由自组装二嵌段共聚物的甲氧基聚（乙二醇）的制备b -聚[3- acrylamidophenylboronic酸共-2-（二乙氨基）乙基甲基丙烯酸酯共-2-羟基4-(甲基丙烯酰氧基)二苯甲酮] (mPEG- b- P(AAPBA- co- DEAEMA- co-BMA)) 通过可逆加成-断裂链转移聚合 (RAFT) 合成，其中胰岛素和葡萄糖氧化酶 (GOx) 被共封装在内部。值得注意的是，具有可调膜渗透性的聚合物囊泡是第一个由 PBA 和 GOx 组成的葡萄糖响应平台。根据葡萄糖酸产生的 pH 变化，pH 敏感单体 DEAEMA 赋予聚合物囊膜多级可调和自我调节的渗透性，进一步控制胰岛素的释放行为。这种多级可调性直接反映在体外胰岛素释放测试中，并通过体内血糖的自我调节得到证实。有希望的是，聚合物囊泡在糖尿病治疗中用于自我调节血糖的潜力巨大。

更新日期：2021-09-13

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