Protection and Systemic Translocation of siRNA Following Oral Administration of Chitosan/siRNA Nanoparticles.
Protection and Systemic Translocation of siRNA Following Oral Administration of Chitosan/siRNA Nanoparticles.
复制标题
DOI：
10.1038/mtna.2013.2
复制
发表时间：
2013-03-05
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
利用RNA干扰途径提供了一种新的治疗方式；然而，临床翻译需要克服小干扰RNA(SiRNA)传递的生物障碍的解决方案。本工作通过直接Northern和定量聚合酶链式反应(QPCR)检测，证明了口服壳聚糖/siRNA纳米粒后，未经修饰的siRNA在小鼠体内的稳定性、胃肠道(GI)沉积和移位。与裸露的siRNA相比，纳米颗粒中的siRNA在1小时和5小时内保留了结构完整性和在胃、近端和远端小肠以及结肠中的沉积。此外，在肠上皮顶端检测到荧光siRNA的组织学检测表明，壳聚糖具有粘附性。灌胃1小时后，观察到肝脏、脾和肾脏中完整的siRNA，其器官分布模式受纳米颗粒N：P比率的影响，反映了颗粒稳定性的差异。这项概念验证工作提供了一个口服给药平台，可能有可能通过siRNA治疗局部和全身疾病。
Harnessing the RNA interference pathway offers a new therapeutic modality; however, solutions to overcome biological barriers to small interfering RNA (siRNA) delivery are required for clinical translation. This work demonstrates, by direct northern and quantitative PCR (qPCR) detection, stability, gastrointestinal (GI) deposition, and translocation into peripheral tissue of nonmodified siRNA after oral gavage of chitosan/siRNA nanoparticles in mice. In contrast to naked siRNA, retained structural integrity and deposition in the stomach, proximal and distal small intestine, and colon was observed at 1 and 5 hours for siRNA within nanoparticles. Furthermore, histological detection of fluorescent siRNA at the apical regions of the intestinal epithelium suggests mucoadhesion provided by chitosan. Detection of intact siRNA in the liver, spleen, and kidney was observed 1 hour after oral gavage, with an organ distribution pattern influenced by nanoparticle N:P ratio that could reflect differences in particle stability. This proof-of-concept work presents an oral delivery platform that could have the potential to treat local and systemic disorders by siRNA.
登录
查看更多内容
影响因子：
12.4
作者：
Howard, Kenneth A.;Rahbek, Ulrik L.;Kjems, Jorgen
通讯作者：
Kjems, Jorgen
影响因子：
3.7
作者：
Nielsen, Ebbe J. B.;Nielsen, Jan M.;Howard, Kenneth A.
通讯作者：
Howard, Kenneth A.
影响因子：
--
作者：
Volkov, Anton A.;Kruglova, Natal'ya S.;Chernolovskaya, Elena L.
通讯作者：
Chernolovskaya, Elena L.
影响因子：
14.9
作者：
Grünweller, A;Wyszko, E;Kurreck, J
通讯作者：
Kurreck, J
影响因子：
5.8
作者：
Soane, RJ;Frier, M;Illum, L
通讯作者：
Illum, L