Controlled release of pioglitazone from biodegradable hydrogels to modify macrophages phenotype

Abstract

Macrophages play a key role in the inflammatory reaction of body defense. It has been demonstrated that there are various types of macrophages and their function greatly affects the progressive conditions of inflammation process. The objective of this study is to develop a drug delivery system (DDS) which can modify the biological function of macrophages. Pioglitazone (Pio) of water-insolubility was water-solubilized by the micelle formation with gelatin grafted with L-lactic acid oligomer (Pio-micelles). The Pio water-solubilized was incorporated into a biodegradable gelatin hydrogel. The experiments of Pio release and hydrogel degradation revealed that pio was released from the hydrogel incorporating Pio-micelles in vitro and in vivo. The Pio-micelles and Pio allowed macrophages to enhance the mRNA expression level of arginase1 which is a measurement of type 2 macrophages. When applied to a skin defect model of mice, the hydrogels incorporating Pio-micelles enhanced the arginase1 level around the site implanted to a significant great extent compared with the Pio solution. The Pio release technique is promising to modify the phenotype of macrophages.