Noncovalenly PEGylated CTGF siRNA/PDMAEMA Complex for Pulmonary Treatment of Bleomycin-Induced Lung Fibrosis

Abstract

On the basis of wide biomedical applications of methacrylate polymers, we previously developed non-covalently post-PEGylated ternary complex of siRNA using poly(dimethylamino)ethylmethacrylate (PDMAEMA) and its copolymer with poly(alpha-methylether-omega-methacrylate-ethyleneglycol) [PMAPEG]. In this work, we investigated the antifibrotic effect of connective tissue growth factor siRNA (siCTGF)/PDMAEMA/PDMAEMA-b-PMAPEG complex for the treatment of bleomycin-induced pulmonary fibrosis. After orotracheal administration to fibrotic Sprague Dawley (SD) model rats, FAM-labeled siCTGF complex was effectively delivered to the cells in the lung. The siCTGF ternary complex resulted in a significant reduction in target gene expression, collagen deposition, inflammatory cytokines production, and drastic attenuation of pulmonary fibrosis in pathophysiological analysis. Furthermore, the survival rate was remarkably increased to the statistically significant level in comparison with the scrambled siCTGF treatment group. (C) 2012 Elsevier Ltd. All rights reserved.