Development and optimization of nanosomal formulations for siRNA delivery to the liver.
Development and optimization of nanosomal formulations for siRNA delivery to the liver.
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DOI：
10.1016/j.ejpb.2011.10.023
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发表时间：
2012-02
期刊：
影响因子：
--
通讯作者：
Mandal TK
中科院分区：
文献类型：
--
作者：
Kundu AK;Chandra PK;Hazari S;Pramar YV;Dash S;Mandal TK
The objective of this study is to develop an effective siRNA delivery system for successful delivery to the liver for the treatment of HCV. Nanosize liposomes (nanosomes) have been prepared using a mixture of cholesterol and DOTAP. A functional siRNA was encapsulated into nanosomes following condensation with protamine sulfate. The delivery of siRNA was optimized in an in vitro cell culture system. The efficacy of the formulations was evaluated by measuring functional gene silencing and cytotoxicity. Encapsulation of siRNA ≥ 7.4 nM resulted in successful delivery of siRNA to nearly 100% of cells. The formulations containing lipids to siRNA ratio ≥ 10.56:1 instantly cleared approximately 85% of HCV while maintaining cell viability at about 90%. The formulations were sonicated to further reduce the particle size. The size of these formulations was decreased up to 100 nm. However, there were no significant changes observed in zeta potential, or in siRNA encapsulation and integrity following sonication. The sonicated formulations also showed higher liver hepatocytes deposition and gene silencing properties. This study therefore provides a novel approach of siRNA delivery to liver hepatocytes which can also be applied to treat HCV in chronic liver diseases.
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影响因子：
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通讯作者：
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