Noncovalenly PEGylated Ternary Complex for Pulmonary Delivery of Therapeutic siRNA

Won Ho Kong, Hyemin Kim, and Sei Kwang Hahn*

Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang, Kyungbuk 790-784, Korea

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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.

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