Noncovalenly PEGylated Ternary Complex for Pulmonary Delivery of Therapeutic siRNA

Category
RNAi and DNA Delivery
Year
2013
Authors
Won Ho Kong, Hyemin Kim, and Sei Kwang Hahn
Institutions
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang, Kyungbuk 790-784, Korea
Summary

We developed non-covalently PEGylated ternary-complex of siRNA using poly(2-dimethylamino)ethyl methacrylate [PDMAEMA] based (co)polymers as a pul-monary delivery carrier of therapeutic siRNA molecules in vivo. After orotracheal instillation to animal models of bleomycin (BLM)-induced pulmonary fibrosis, the ter-nary (t) complexes of connective tissue growth factor siRNA (siCTGF) were effectively delivered to the cells in the lung. Accordingly, the treatment resulted in a signifi-cant reduction in target gene expression, collagen deposi-tion, inflammatory cytokines production, and drastic at-tenuation of pulmonary fibrosis in pathophysiological analysis. Moreover, the survival rate was remarkably in-creased to the statistically significant level in comparison with the scrambled siRNA treatment group.