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

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.

Keywords: boronic acid; gel; injectable material; insulin; stimulus-responsive; worm-like micelles.

MeSH terms

  • Blood Glucose / chemistry*
  • Boronic Acids / chemistry
  • Cetrimonium / chemistry
  • Dextrans / administration & dosage
  • Dextrans / pharmacokinetics
  • Drug Delivery Systems / methods*
  • Drug Liberation*
  • Fluorescein-5-isothiocyanate / administration & dosage
  • Fluorescein-5-isothiocyanate / analogs & derivatives
  • Fluorescein-5-isothiocyanate / pharmacokinetics
  • Gels / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Hypoglycemia / blood
  • Hypoglycemia / drug therapy*
  • Hypoglycemic Agents / administration & dosage
  • Insulin / administration & dosage
  • Micelles*
  • Viscosity / drug effects
  • Water / chemistry

Substances

  • Blood Glucose
  • Boronic Acids
  • Dextrans
  • Gels
  • Hypoglycemic Agents
  • Insulin
  • Micelles
  • fluorescein isothiocyanate dextran
  • Water
  • Fluorescein-5-isothiocyanate
  • benzeneboronic acid
  • Cetrimonium