Long-Acting Release Formulation of Exendin-4 Based on Biomimetic Mineralization for Type 2 Diabetes Therapy.

Abstract

Exendin-4 has been clinically exploited for treating type 2 diabetes, but the short circulation half-life and multiple daily injections limit its widespread application with respect to poor patient compliance, low efficacy, and high treatment cost. In this study, a potent long-acting release system based on biomimetic mineralization was constructed for biocompatible and sustained exendin-4 delivery. Similar to natural biomineralization, exendin-4 can be mineralized to form nanosized mineral solids by means of the reaction between acidic amino acid residues and calcium ions in a supersaturated environment with negligible influence on peptide bioactivity. Mineralized exendin-4 particles may be spontaneously absorbed by a living body under physiologically supersaturated conditions, resulting in gradual dissociation and sustained drug release. In such a way, the glucose level of diabetic mice may be effectively controlled for a long period of time by mineralized exendin-4 without obvious side effects. We believe this biomimetic formulation can serve as a promising candidate for future clinical applications for type 2 diabetes therapies.

• Authors: Wei Chen, Guohao Wang, Bryant C Yung, Gang Liu, Zhiyong Qian, Xiaoyuan Chen
• Journal: ACS nano (ACS Nano) Vol. 11 Issue 5 Pg. 5062-5069 (05 23 2017) ISSN: 1936-086X [Electronic] United States
• PMID: 28437610 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Delayed-Action Preparations
• Hypoglycemic Agents
• Insulin
• Peptides
• Exenatide

Topics

• Animals
• Biomimetic Materials
• Biomimetics (methods)
• Biomineralization (drug effects)
• Blood Glucose (metabolism)
• Delayed-Action Preparations (chemistry, pharmacology)
• Diabetes Mellitus, Experimental (drug therapy)
• Diabetes Mellitus, Type 2 (therapy)
• Exenatide (administration & dosage, pharmacology)
• Hypoglycemic Agents (chemistry)
• Insulin (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Peptides (chemistry)