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新型蠕虫状胶束凝胶在十六烷基三甲基溴化铵/苯硼酸/水体系中的葡萄糖响应流变变化和药物释放。

Glucose Responsive Rheological Change and Drug Release from a Novel Worm-like Micelle Gel Formed in Cetyltrimethylammonium Bromide/Phenylboronic Acid/Water System.

机构信息

Faculty of Pharmacy and Pharmaceutical Sciences , Josai University , 1-1 Keyakidai , Sakado , Saitama 350-0295 , Japan.

Faculty of Pharmaceutical Sciences , Sojo University , 4-22-1 Ikeda , Nishi-ku, Kumamoto 860-0082 , Japan.

出版信息

Mol Pharm. 2018 Mar 5;15(3):1097-1104. doi: 10.1021/acs.molpharmaceut.7b00988. Epub 2018 Feb 7.

Abstract

A novel glucose (Glc)-responsive gel formed by worm-like micelles (WLMs) has the potential to provide a self-regulating insulin delivery system. We have prepared a WLM gel system using 75 mM cetyltrimethylammonium bromide, 75 mM phenylboronic acid, and water. At pH 9.4, this gel-like system was highly viscous and supported its own weight, and dynamic viscoelasticity measurement indicated that it contained long and entangled WLMs. The visual observation of gels prepared to include >6 mM Glc revealed that these adopted a sol-like appearance, whereas those prepared to include a control compound (2-10 mM diethylene glycol) retained their gel-like appearance. The storage modulus ( G') of this system decreased as the Glc concentration increased (2-10 mM), indicating a gradual shortening of the WLMs. In vitro release was evaluated using a test compound (fluorescein isothiocyanate dextran) in a microsized flow system. By 120 min, the release of this compound from the WLM gel was around 27-fold greater in the presence of 100 mM Glc than without Glc or with 100 mM diethylene glycol. This demonstrated the successful preparation of a WLM gel that showed an altered drug release rate, depending on Glc concentration.

摘要

一种新型的葡萄糖(Glc)响应凝胶由蠕虫状胶束(WLMs)形成,有可能提供一种自调节的胰岛素递送系统。我们使用 75mM 十六烷基三甲基溴化铵、75mM 苯硼酸和水制备了一种 WLMs 凝胶系统。在 pH9.4 时,这种凝胶状系统具有很高的粘性,能够支撑自身重量,动态粘弹性测量表明它含有长而缠结的 WLMs。对包含>6mMGlc 的凝胶的目视观察表明,这些凝胶呈溶胶状外观,而那些包含对照化合物(2-10mM 二乙二醇)的凝胶则保持凝胶状外观。随着 Glc 浓度的增加(2-10mM),该系统的储能模量(G')降低,表明 WLMs 逐渐缩短。使用微流系统中的测试化合物(异硫氰酸荧光素葡聚糖)评估了体外释放情况。在 120 分钟时,在存在 100mMGlc 的情况下,这种化合物从 WLMs 凝胶中的释放量比没有 Glc 或有 100mM 二乙二醇时增加了约 27 倍。这证明了成功制备了一种 WLMs 凝胶,该凝胶的药物释放速率可以根据 Glc 浓度进行改变。

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