Localized Delivery of Antisense Oligonucleotides by Cationic Hydrogel Suppresses TNF-α Expression and Endotoxin-Induced Osteolysis
| Autor: | Lei Dong, Junfeng Zhang, Xing Cai, Yi'an Zhu, Jiangning Chen, Zhen Huang, Rui Wang, Jiawei Xiang |
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| Rok vydání: | 2010 |
| Předmět: |
Osteolysis
Bone disease Pharmaceutical Science Gene delivery Hydrogel Polyethylene Glycol Dimethacrylate Bone resorption Rats Sprague-Dawley Chitosan Mice chemistry.chemical_compound Drug Delivery Systems Osteogenesis In vivo Cations medicine Animals Pharmacology (medical) Pharmacology Tumor Necrosis Factor-alpha Chemistry Organic Chemistry Gene Transfer Techniques Genetic Therapy Oligonucleotides Antisense medicine.disease Molecular biology In vitro Rats Endotoxins Mice Inbred C57BL Drug delivery Cancer research Gelatin Molecular Medicine Female Biotechnology |
| Zdroj: | Pharmaceutical Research. 28:1349-1356 |
| ISSN: | 1573-904X 0724-8741 |
| Popis: | To investigate the possibility of using localized nucleic drug delivery methods for the treatment of osteolysis-related bone disease. 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. 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. This is a successful attempt to apply localized gene delivery method to treat inflammatory diseases in vivo. |
| Databáze: | OpenAIRE |
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