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Title: Early controlled release of peroxisome proliferator-activated receptor β/δ agonist GW501516 improves diabetic wound healing through redox modulation of wound microenvironment
Authors: Choong, Cleo Swee Neo
Tan, Nguan Soon
Wang, Xiaoling
Sng, Ming Keat
Foo, Selin
Chong, Han Chung
Lee, Wei Li
Tang, Mark Boon Yang
Ng, Kee Woei
Luo, Baiwen
Wong, Marcus Thien Chong
Tong, Benny Meng Kiat
Chiba, Shunsuke
Loo, Say Chye Joachim
Zhu, Pengcheng
Keywords: DRNTU::Science::Biological sciences::Human anatomy and physiology
Issue Date: 2015
Source: Wang, X., Sng, M. K., Foo, S., Chong, H. C., Lee, W. L., Tang, M. B. Y., et al. (2014). Early controlled release of peroxisome proliferator-activated receptor β/δ agonist GW501516 improves diabetic wound healing through redox modulation of wound microenvironment. Journal of controlled release, 197, 138-147.
Series/Report no.: Journal of controlled release
Abstract: Diabetic wounds are imbued with an early excessive and protracted reactive oxygen species production. Despite the studies supporting PPARβ/δ as a valuable pharmacologic wound-healing target, the therapeutic potential of PPARβ/δ agonist GW501516 (GW) as a wound healing drug was never investigated. Using topical application of polymer-encapsulated GW, we revealed that different drug release profiles can significantly influence the therapeutic efficacy of GW and consequently diabetic wound closure. We showed that double-layer encapsulated GW microparticles (PLLA:PLGA:GW) provided an earlier and sustained dose of GW to the wound and reduced the oxidative wound microenvironment to accelerate healing, in contrast to single-layered PLLA:GW microparticles. The underlying mechanism involved an early GW-mediated activation of PPARβ/δ that stimulated GPx1 and catalase expression in fibroblasts. GPx1 and catalase scavenged excessive H2O2 accumulation in diabetic wound beds, prevented H2O2-induced ECM modification and facilitated keratinocyte migration. The microparticles with early and sustained rate of GW release had better therapeutic wound healing activity. The present study underscores the importance of drug release kinetics on the therapeutic efficacy of the drug and warrants investigations to better appreciate the full potential of controlled drug release.
ISSN: 0168-3659
DOI: 10.1016/j.jconrel.2014.11.001
Rights: © 2014 Elsevier. This is the author created version of a work that has been peer reviewed and accepted for publication by Journal of Controlled Release, Elsevier. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:MSE Journal Articles
SBS Journal Articles
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