In vitro and in vivo evaluation of thermosensitive chitosan hydrogel for sustained release of insulin

Drug Deliv. 2016;23(3):1038-46. doi: 10.3109/10717544.2014.932861. Epub 2014 Jul 9.

Abstract

Injectable In situ gel-forming chitosan/β-glycerol phosphate (CS/β-Gp) solution can be introduced into the body in a minimally invasive manner prior to solidifying within the target tissue. This hydrogel is a good candidate for achieving a prolonged drug delivery system for insulin considering its high molecular weight. In addition to the physicochemical characterization of this hydrogel, in vitro and in vivo applications were studied as a sustained insulin delivery system. In the in vitro release studies, 19-63% of total insulin was released from the CS/β-Gp hydrogel within 150 h at different β-Gp and insulin concentrations. The best formulation was selected for in vivo experimentation to control the plasma glucose of diabetic mice models. The hypoglycemic effect of this formulation following subcutaneous injection in diabetic mice lasted 5 d, significantly longer than that of free insulin solution which lasted several hours.

Keywords: diabetic mice; in situ gel-forming; injectable; subcutaneous injection; β-glycerolphopshate.

MeSH terms

  • Animals
  • Chemistry, Pharmaceutical / methods
  • Chitosan / chemistry*
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemistry*
  • Delayed-Action Preparations / pharmacokinetics*
  • Diabetes Mellitus, Experimental / drug therapy
  • Drug Delivery Systems / methods
  • Glycerophosphates / chemistry
  • Hydrogel, Polyethylene Glycol Dimethacrylate / administration & dosage
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry*
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacokinetics*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacokinetics
  • Insulin / administration & dosage
  • Insulin / chemistry*
  • Insulin / pharmacokinetics*
  • Mice
  • Pharmaceutical Solutions / administration & dosage
  • Pharmaceutical Solutions / chemistry
  • Pharmaceutical Solutions / pharmacokinetics
  • Temperature

Substances

  • Delayed-Action Preparations
  • Glycerophosphates
  • Hypoglycemic Agents
  • Insulin
  • Pharmaceutical Solutions
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Chitosan
  • beta-glycerophosphoric acid