阳离子水凝胶局部递送达抗 TNF-α 寡核苷酸可抑制 TNF-α 表达和内毒素诱导的骨溶解。
Localized delivery of antisense oligonucleotides by cationic hydrogel suppresses TNF-α expression and endotoxin-induced osteolysis.
机构信息
State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, Nanjing 210093, China.
出版信息
Pharm Res. 2011 Jun;28(6):1349-56. doi: 10.1007/s11095-010-0334-0. Epub 2010 Dec 8.
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.
目的
研究局部核酸药物传递方法治疗与骨溶解相关的骨疾病的可能性。
方法
采用由明胶和壳聚糖组成的可生物降解阳离子水凝胶，传递针对鼠 TNF-α 的反义寡核苷酸（ASO），以治疗内毒素诱导的骨溶解。
结果
当附着细胞消化时，与该水凝胶结合的 ASO 被释放。体外和体内实验结果表明，释放的 ASO 可有效地递送到接触的细胞和组织中。在内毒素诱导的骨吸收动物模型中进行测试时，通过这种方式递送的 ASO 可有效抑制 TNF-α 的表达，进而抑制体内破骨细胞的生成。内毒素诱导的骨吸收动物模型中的骨溶解被治疗所阻断。
结论
这是成功尝试将局部基因传递方法应用于治疗体内炎症性疾病。
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