caa a22 4500 445311851 CHVBK 20180317142632.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s11095-010-0334-0 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0334-0 Localized Delivery of Antisense Oligonucleotides by Cationic Hydrogel Suppresses TNF-α Expression and Endotoxin-Induced Osteolysis [Elektronische Daten] [Lei Dong, Zhen Huang, Xing Cai, Jiawei Xiang, Yi-An Zhu, Rui Wang, Jiangning Chen, Junfeng Zhang] ABSTRACT: Purpose: To investigate the possibility of using localized nucleic drug delivery methods for the treatment of osteolysis-related bone disease. Methods: A bio-degradable cationic hydrogel composed of gelatin and chitosan was used to deliver an antisense oligonucleotide (ASO) targeting murine TNF-α for the treatment of endotoxin-induced osteolysis. Results: ASO combined with this hydrogel was released when it was digested by adhering cells. The released ASO was efficiently delivered into contacted cells and tissues in vitro and in vivo. When tested in animal models of edotoxin-induced bone resorption, ASO delivered by such means effectively suppressed the expression of TNF-α and subsequently the osteoclastogenesis in vivo. Osteolysis in the edotoxin-induced bone resorption animal models was blocked by the treatment. Conclusion: This is a successful attempt to apply localized gene delivery method to treat inflammatory diseases in vivo. Springer Science+Business Media, LLC, 2010 antisense nationallicence localized gene delivery nationallicence osteolysis nationallicence TNF-α nationallicence Dong Lei State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, 210093, Nanjing, China aut Huang Zhen State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, 210093, Nanjing, China aut Cai Xing State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, 210093, Nanjing, China aut Xiang Jiawei State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, 210093, Nanjing, China aut Zhu Yi-An State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, 210093, Nanjing, China aut Wang Rui Department of Orthopaedics, Jinling Hospital, School of Medicine, Nanjing University, 210093, Nanjing, China aut Chen Jiangning State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, 210093, Nanjing, China aut Zhang Junfeng State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, 210093, Nanjing, China aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/6(2011-06-01), 1349-1356 0724-8741 28:6<1349 2011 28 11095 https://doi.org/10.1007/s11095-010-0334-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0334-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Dong Lei State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, 210093, Nanjing, China aut NATIONALLICENCE 700 1- Huang Zhen State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, 210093, Nanjing, China aut NATIONALLICENCE 700 1- Cai Xing State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, 210093, Nanjing, China aut NATIONALLICENCE 700 1- Xiang Jiawei State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, 210093, Nanjing, China aut NATIONALLICENCE 700 1- Zhu Yi-An State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, 210093, Nanjing, China aut NATIONALLICENCE 700 1- Wang Rui Department of Orthopaedics, Jinling Hospital, School of Medicine, Nanjing University, 210093, Nanjing, China aut NATIONALLICENCE 700 1- Chen Jiangning State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, 210093, Nanjing, China aut NATIONALLICENCE 700 1- Zhang Junfeng State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, 210093, Nanjing, China aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/6(2011-06-01), 1349-1356 0724-8741 28:6<1349 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer