In Vivo Sustained Release of siRNA from Solid Lipid Nanoparticles

被引：117

作者：

Lobovkina, Tatsiana ^{[1
]}

Jacobson, Gunilla B. ^{[1
]}

Gonzalez-Gonzalez, Emilio ^{[2
,3
]}

Hickerson, Robyn P. ^{[4
]}

Leake, Devin ^{[5
]}

Kaspar, Roger L. ^{[2
,4
]}

Contag, Christopher H. ^{[2
,3
,6
,7
]}

Zare, Richard N. ^{[1
]}

机构：

[1] Stanford Univ, Dept Chem, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA

[3] Stanford Univ, Mol Imaging Program, Stanford, CA 94305 USA

[4] TransDerm Inc, Santa Cruz, CA 95060 USA

[5] Thermo Fisher Sci, Dharmacon Prod, Lafayette, CO 80026 USA

[6] Stanford Univ, Dept Radiol, Sch Med, Stanford, CA 94305 USA

[7] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA

来源：

ACS NANO | 2011年 / 5卷 / 12期

基金：

美国国家科学基金会;

关键词：

solid lipid nanoparticles; siRNA; sustained release; drug delivery; SMALL-INTERFERING RNA; CORE-SHELL NANOPARTICLES; DRUG-DELIVERY; POLYMERIC NANOPARTICLES; PLASMID DNA; SKIN MODEL; EXPRESSION; KINETICS; SYSTEM;

D O I：

10.1021/nn203745n

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Small interfering RNA (siRNA) Is a highly potent drug in gene-based therapy with a challenge of being delivered In a sustained manner. Nanoparticle drug delivery systems allow for Incorporating and controlled release of therapeutic payloads. We demonstrate that solid lipid nanoparticles can incorporate and provide sustained release of siRNA. Tristearin solid lipid nanoparticles, made by nanoprecipitation, were loaded with siRNA (4.4-5.5 wt % loading ratio) using a hydrophobic ion pairing approach that employs the cationic lipid DOTAP. Intradermal Injection of these nanocarriers in mouse footpads resulted In prolonged siRNA release over a period of 10-13 days. In vitro cell studies showed that the released siRNA retained its activity. Nanoparticles developed in this study offer an alternative approach to polymeric nanoparticles for encapsulation and sustained delivery of siRNA with the advantage of being prepared from physiologically well-tolerated materials.

引用

页码：9977 / 9983

页数：7

共 41 条

[1] Factors affecting the clearance and biodistribution of polymeric nanoparticles [J].