Smarter glucose-sensitivity of polymeric micelles formed from phenylborate ester-co-pyrenylboronic ester for insulin delivery at physiological pH
Smarter glucose-sensitivity of polymeric micelles formed from phenylborate ester-co-pyrenylboronic ester for insulin delivery at physiological pH
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由苯硼酸酯-芘基硼酸酯形成的聚合物胶束具有更智能的葡萄糖敏感性，用于在生理 pH 值下输送胰岛素
DOI：
10.1039/c4ra08593k
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发表时间：
2014-10
期刊：
影响因子：
3.9
通讯作者：
Yang, Jing
中科院分区：
文献类型：
--
作者：
Zhang, Xuan;Shen, Heyun;Yang, Junjiao;Yang, Jing
探索能够响应葡萄糖水平变化释放胰岛素的智能系统将提高糖尿病的治疗潜力。在此，我们开发了一种分散的葡萄糖响应组策略，以有效地增强系统的葡萄糖敏感性，以响应生理需要而自我调节胰岛素的递送。以聚乙二醇（PEG）5000-Br为大分子引发剂，通过一步原子转移自由基聚合（ATRP），合成了一种两亲性嵌段聚合物，命名为聚乙二醇-嵌段-聚[（2-苯基硼酸酯-1，3-二氧六环-5-乙基）甲基丙烯酸酯-co-（2-芘基硼酸酯-1，3-二氧六环-5-乙基）甲基丙烯酸酯] MPEG-b-P（PBDEMA-co-PyBDEMA）。这些两亲性聚合物MPEG-b-P（PBDEMA-co-PyBDEMA）自组装形成具有由葡萄糖响应性PPBDEMA和强疏水性PPyBDEMA组成的疏水核的聚合物胶束。结果，在pH 7.4下，这些聚合物胶束在葡萄糖浓度为1.0 mg mL-1（血糖正常）时表现出非常缓慢的胰岛素释放，而在3.0 mg mL-1（高血糖）时表现出相对快速的释放行为。此外，在pH 7.4下，用1.0和3.0 mg mL-1葡萄糖交替孵育进一步研究了葡萄糖触发的胰岛素开关释放，以显示响应生理葡萄糖水平波动的有效自我调节胰岛素递送。此外，胰岛素的包封率（EE）和负载量（LC）也明显提高，分别接近65%和20%。这种类型的纳米载体可能是一个有前途的候选人在体内胰岛素输送。
Exploring an intelligent system capable of releasing insulin in response to glucose level changes would improve the therapeutic potential in diabetes. Herein, we developed a dispersing glucose-responsive group strategy to effectively enhance glucose-sensitivity of the system for the self-regulated delivery of insulin in response to physiological need. One kind of amphiphilic block polymer, which was named poly(ethylene glycol)-block-poly[(2-phenyl boronic esters-1,3-dioxane-5-ethyl) methylacrylate-co-(2-pyrenyl boronic esters-1,3-dioxane-5-ethyl) methylacrylate] MPEG-b-P(PBDEMA-co-PyBDEMA), was fabricated by one-step atom transfer radical polymerization (ATRP) of two monomers PBDEMA and PyBDEMA with MPEG5000-Br as a macroinitiator. These amphiphilic polymers MPEG-b-P(PBDEMA-co-PyBDEMA) were self-assembled to form polymeric micelles with a hydrophobic core composed of both glucose-responsive PPBDEMA and strongly hydrophobic PPyBDEMA. As a result, these polymeric micelles exhibited very slow insulin release at glucose concentration of 1.0 mg mL−1 (normoglycemia) and relatively rapid release behavior at 3.0 mg mL−1 (hyperglycemia) at pH 7.4. Moreover, the glucose-triggered on-off release of insulin was further investigated at pH 7.4 with alternate 1.0 and 3.0 mg mL−1 glucose incubation to exhibit an effective self-regulated insulin delivery in response to physiological glucose level fluctuation. In addition, the encapsulation efficiency (EE) and loading capacity (LC) of insulin were distinctly enhanced to nearly 65% and 20%, respectively. This type of nanocarrier may be a promising candidate for in vivo insulin delivery.
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影响因子：
6.2
作者：
Matsumoto, A;Yoshida, R;Kataoka, K
通讯作者：
Kataoka, K
影响因子：
3.4
作者：
Cui Cheng;Xinge Zhang;Jixin Xiang;Yanxia Wang;C. Zheng;Zhentan Lu;Chaoxing Li
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van Hest, Jan C. M.
影响因子：
17.1
作者：
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通讯作者：
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影响因子：
10
作者：
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通讯作者：
Anderson, Daniel G.