title: Local release of pioglitazone (a peroxisome proliferator-activated receptor γ agonist) accelerates proliferation and remodeling phases of wound healing.
abstract: Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily known for its anti-inflammatory and macrophage differentiation effects, as well as its ability to promote fat cell differentiation and reduce insulin resistance. Pioglitazone (Pio) is a PPARγ agonist used clinically as an anti-diabetic agent for improving insulin sensitivity in patients with diabetes. The objective of this study was to develop a drug delivery system (DDS) for the local release of Pio to promote wound healing. Pio of low aqueous solubility was water-solubilized by micelles formed from gelatin grafted with L-lactic acid oligomers, and incorporated into a biodegradable gelatin hydrogel. An 8-mm punch biopsy tool was used to prepare two skin wounds on either side of the midline of 8-week-old mice. Wounds were treated by the hydrogels with (Pio-hydrogel group) or without (control group) Pio, and the wound area were observed 1, 4, 7, and 14 days after treatment. In addition, a protein assay and immunohistological stain were performed to determine the effects of the Pio-hydrogel on inflammation and macrophage differentiation. The Pio-hydrogels promote wound healing. Moreover, Western blotting analysis demonstrated that treatment with Pio-hydrogels resulted in decreased levels of the cytokines MIP-2 and TGF-β, and increased levels of glucose-regulating adiponectin. It is concluded that Pio-incorporated hydrogels promote the proliferation and remodeling phases of wound healing, and may prove to be effective as wound dressings.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo, 160-8582, Japan.|Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo, 160-8582, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kishi
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D047070:Bandages, Hydrocolloid; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D054426:Chemokine CXCL2 / Q000187:drug effects / Q000276:immunology; D016503:Drug Delivery Systems; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D007333:Insulin Resistance; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008823:Micelles; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000276:immunology; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology
chemical_list: D052242:Adiponectin; D054426:Chemokine CXCL2; D007004:Hypoglycemic Agents; D008823:Micelles; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; D000077205:Pioglitazone
keywords: PPARγ; diabetes; hydrogel; pioglitazone; wound covering material; wound healing