Effect of topical application of encapsulated PPARbeta/delta agonist GW501516 microparticles, with two release kinetics, on cutaneous wound healing in diabetic mice -a preclinical animal study.

Wound complications in diabetic patients present therapeutic problems of increasing clinical importance. Despite the compelling evidence for a role of PPARß/d in wound healing, using PPARß/d agonists as pharmacological agents in the treatment of diabetic wound healing remain to be justified. Using the genetically and high-fat diet-induced diabetic mice as a model of impaired wound healing, we will perform a preclinical study of the effect of topical application of PPARß/d agonist GW501516 on the healing of full-thickness wounds. We will chemically synthesize and encapsulate GW501516 into single- and double-walled spherical microparticles to achieve early and sustained release, respectively. This method of drug delivery is novel with respect to PPARß/d research, and it allows the pharmacokinetics and pharmacodynamics of the drug to be controlled more effectively and selectively. Topical application of encapsulated agonists was chosen as the method of delivery because of its clinical practicability. This delivery method results in non-systemic exposure to the drug and thereby establishes a more favorable safety profile of the drug. At various days post-treatment, detail wound healing review that includes inflammatory response, rate of re-epithelialization, scarring and angiogenesis assessment will be performed. A focused real-time PCR array of the wound biopsies will also be performed to provide holistic perspective on the effect of the various treatments. To adopt an evidence-based wound care practice, it is imperative to obtain information pertaining to changes in gene expression during the healing of human acute wound. Although such information would validate our current findings, more importantly, it will provide the pertinent information for future human wound care management. The findings from this project will enable the further advancement and development of novel therapeutic options for patients with chronic diabetic wounds. This study will lead to future clinical advancement and development of novel drug delivery systems.