Effect of topical soluble epoxide hydrolase inhibition in a preclinical diabetic wound healing model.

Abstract

The objective of this study was to test a topical formulation of EPHX2 inhibitor, GSK2256294, in a dermal wound diabetic (db/db) mouse model. Comparisons were made between groups treated with EPHX2 inhibitor, matching vehicle control and a currently approved treatment for diabetic ulcers, becaplermin/Regranex, as a positive control which is highly efficacious in this model. Leptin receptor-deficient (db/db) male mice were sequentially assigned to treatment groups (N=10 per group) based on blood glucose levels and body weight. Mice were given a single 8 mm diameter full thickness wound on the back. Wounds were photographed and traced, and fresh test materials applied periodically with fresh dressing. Of ten mice treated with GSK2256294, three had completely healed wounds at the study conclusion, and 8/10 mice reached at least 50% closure. In the vehicle group, no mice achieved complete closure, and only 6/10 reached at least 50% closure by the study conclusion. Nine of ten wounds achieved complete closure in the positive control group by 21 days. Although the EPHX2 inhibitor results were indicative of efficacy, the single-sided p-value criterion of 0.05 was not met in this study.