Oral delivery of insulin using pH-responsive complexation gels

J Pharm Sci. 1999 Sep;88(9):933-7. doi: 10.1021/js980337n.

Abstract

The goal of oral insulin delivery devices is to protect the sensitive drug from proteolytic degradation in the stomach and upper portion of the small intestine. In this work, we investigate the use of pH-responsive, poly(methacrylic-g-ethylene glycol) hydrogels as oral delivery vehicles for insulin. Insulin was loaded into polymeric microspheres and administered orally to healthy and diabetic Wistar rats. In the acidic environment of the stomach, the gels were unswollen due to the formation of intermolecular polymer complexes. The insulin remained in the gel and was protected from proteolytic degradation. In the basic and neutral environments of the intestine, the complexes dissociated which resulted in rapid gel swelling and insulin release. Within 2 h of administration of the insulin-containing polymers, strong dose-dependent hypoglycemic effects were observed in both healthy and diabetic rats. These effects lasted for up to 8 h following administration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Area Under Curve
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy
  • Hydrogels
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacokinetics*
  • Insulin / administration & dosage
  • Insulin / chemistry
  • Insulin / pharmacokinetics*
  • Male
  • Methacrylates
  • Microspheres
  • Pharmaceutic Aids
  • Polyethylene Glycols
  • Rats
  • Rats, Wistar

Substances

  • Blood Glucose
  • Hydrogels
  • Hypoglycemic Agents
  • Insulin
  • Methacrylates
  • Pharmaceutic Aids
  • Polyethylene Glycols