Early controlled release of peroxisome proliferator-activated receptor β/δ agonist GW501516 improves diabetic wound healing through redox modulation of wound microenvironment
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. Us...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2015
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| Online Access: | https://hdl.handle.net/10356/100134 http://hdl.handle.net/10220/25674 |
| _version_ | 1826119995934900224 |
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| author | 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 |
| author2 | School of Materials Science & Engineering |
| author_facet | School of Materials Science & Engineering 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 |
| author_sort | Choong, Cleo Swee Neo |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T05:09:17Z |
| format | Journal Article |
| id | ntu-10356/100134 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:09:17Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/1001342023-02-28T17:02:33Z Early controlled release of peroxisome proliferator-activated receptor β/δ agonist GW501516 improves diabetic wound healing through redox modulation of wound microenvironment 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 School of Materials Science & Engineering School of Biological Sciences School of Physical and Mathematical Sciences DRNTU::Science::Biological sciences::Human anatomy and physiology 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. Accepted version 2015-05-26T01:02:54Z 2019-12-06T20:17:16Z 2015-05-26T01:02:54Z 2019-12-06T20:17:16Z 2015 2015 Journal Article 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. 0168-3659 https://hdl.handle.net/10356/100134 http://hdl.handle.net/10220/25674 10.1016/j.jconrel.2014.11.001 en Journal of controlled release © 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: [http://dx.doi.org/10.1016/j.jconrel.2014.11.001]. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences::Human anatomy and physiology 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 Early controlled release of peroxisome proliferator-activated receptor β/δ agonist GW501516 improves diabetic wound healing through redox modulation of wound microenvironment |
| title | Early controlled release of peroxisome proliferator-activated receptor β/δ agonist GW501516 improves diabetic wound healing through redox modulation of wound microenvironment |
| title_full | Early controlled release of peroxisome proliferator-activated receptor β/δ agonist GW501516 improves diabetic wound healing through redox modulation of wound microenvironment |
| title_fullStr | Early controlled release of peroxisome proliferator-activated receptor β/δ agonist GW501516 improves diabetic wound healing through redox modulation of wound microenvironment |
| title_full_unstemmed | Early controlled release of peroxisome proliferator-activated receptor β/δ agonist GW501516 improves diabetic wound healing through redox modulation of wound microenvironment |
| title_short | Early controlled release of peroxisome proliferator-activated receptor β/δ agonist GW501516 improves diabetic wound healing through redox modulation of wound microenvironment |
| title_sort | early controlled release of peroxisome proliferator activated receptor β δ agonist gw501516 improves diabetic wound healing through redox modulation of wound microenvironment |
| topic | DRNTU::Science::Biological sciences::Human anatomy and physiology |
| url | https://hdl.handle.net/10356/100134 http://hdl.handle.net/10220/25674 |
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