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Local release of pioglitazone (a peroxisome proliferator‐activated receptor γ agonist) accelerates proliferation and remodeling phases of wound healing
Author(s) -
Sakai Shigeki,
Sato Keisuke,
Tabata Yasuhiko,
Kishi Kazuo
Publication year - 2015
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/wrr.12376
Subject(s) - pioglitazone , wound healing , self healing hydrogels , chemistry , inflammation , agonist , receptor , pharmacology , gelatin , endocrinology , medicine , biochemistry , diabetes mellitus , type 2 diabetes , surgery , organic chemistry
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.