A novel drug delivery system for type 1 diabetes: insulin-mimetic vanadyl-poly(gamma-glutamic acid) complex.

Abstract

Insulin-mimetic vanadyl-poly(gamma-glutamic acid) complex, VO-gamma-PGA, is proposed as a novel drug delivery system for treating type 1 diabetic animals. The structure of VO-gamma-PGA in solution as well as in solid state was analyzed by electronic absorption, infra-red, and electron spin resonance spectra, and proposed that the equatorial coordination mode of VO(2+) is in either carboxylate(O)-VO-(OH(2))(3) or 2 carboxylate(O(2))-VO-(OH(2))(2). In vitro insulin-mimetic activity, metallokinetic feature in the blood of healthy rats, and in vivo normoglycemic effect of the complex prepared in solution were evaluated in streptozotocin(STZ)-induced type 1 diabetic mice, and these effects were compared with those of a solution containing only VOSO(4) as a positive control. The in vitro insulin-mimetic activity of VO-gamma-PGA was examined by determining both inhibition of free fatty acid (FFA) release and glucose uptake in isolated rat adipocytes, in which the concentration of VO-gamma-PGA for 50% inhibition of FFA release was significantly lower than that of VOSO(4). Metallokinetic study suggested that the bioavailability of VO-gamma-PGA complex was much higher than that of VOSO(4). The complex showed a significant hypoglycemic activity within at least 4h after a single oral administration, the effect being sustained for at least 24h. Furthermore, VO-gamma-PGA normalized the hyperglycemia in STZ-mice within 3 days when it was given orally at doses of 5-10mgVkg(-1) body mass for 16 days. The improvement in diabetes was also supported by the results on oral glucose tolerance test, HbA(1c) levels, and blood pressure.

• Authors: Subarna Karmaker, Tapan K Saha, Yutaka Yoshikawa, Hiroyuki Yasui, Hiromu Sakurai
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 100 Issue 9 Pg. 1535-46 (Sep 2006) ISSN: 0162-0134 [Print] United States
• PMID: 16824605 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hypoglycemic Agents
• Insulin
• Vanadium
• Glutamic Acid

Topics

• Animals
• Diabetes Mellitus, Experimental
• Diabetes Mellitus, Type 1 (therapy)
• Drug Delivery Systems (methods)
• Glutamic Acid (administration & dosage)
• Hypoglycemic Agents (administration & dosage)
• Insulin (administration & dosage, analogs & derivatives, chemistry)
• Mice
• Molecular Structure
• Vanadium (chemistry)