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Early controlled release of peroxisome proliferator-activated receptor ß/δ agonist GW501516 improves diabetic wound healing through redox modulation of wound microenvironment.
Wang, Xiaoling; Sng, Ming Keat; Foo, Selin; Chong, Han Chung; Lee, Wei Li; Tang, Mark Boon Yang; Ng, Kee Woei; Luo, Baiwen; Choong, Cleo; Wong, Marcus Thien Chong; Tong, Benny Meng Kiat; Chiba, Shunsuke; Loo, Say Chye Joachim; Zhu, Pengcheng; Tan, Nguan Soon.
Affiliation
  • Wang X; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
  • Sng MK; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
  • Foo S; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
  • Chong HC; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
  • Lee WL; School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798.
  • Tang MB; National Skin Centre, 1 Mandalay Road, Singapore 308205.
  • Ng KW; School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798.
  • Luo B; School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798.
  • Choong C; School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798.
  • Wong MT; Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433.
  • Tong BM; Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371.
  • Chiba S; Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371.
  • Loo SC; School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798.
  • Zhu P; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551. Electronic address: pczhu@ntu.edu.sg.
  • Tan NS; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551; Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673. Electronic address: nstan@ntu.edu.sg.
J Control Release ; 197: 138-47, 2015 Jan 10.
Article in En | MEDLINE | ID: mdl-25449811
Diabetic wounds are imbued with an early excessive and protracted reactive oxygen species production. Despite the studies supporting PPARß/δ as a valuable pharmacologic wound-healing target, the therapeutic potential of PPARß/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 PPARß/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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Thiazoles / Wound Healing / Drug Delivery Systems / PPAR-beta / PPAR delta Limits: Animals / Humans / Male Language: En Journal: J Control Release Journal subject: FARMACOLOGIA Year: 2015 Document type: Article Country of publication: Netherlands

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Thiazoles / Wound Healing / Drug Delivery Systems / PPAR-beta / PPAR delta Limits: Animals / Humans / Male Language: En Journal: J Control Release Journal subject: FARMACOLOGIA Year: 2015 Document type: Article Country of publication: Netherlands