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

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posted on 2018-02-07, 15:36 authored by Ryotaro Miki, Chihiro Takei, Yasushi Ohtani, Kosuke Kawashima, Ayaka Yoshida, Yu Kojima, Yuya Egawa, Toshinobu Seki, Daisuke Iohara, Makoto Anraku, Fumitoshi Hirayama, Kaneto Uekama
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.

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