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Mol Pharm. 2008 Jul-Aug;5(4):622-31. doi: 10.1021/mp8000233. Epub 2008 May 8.

Cationic solid lipid nanoparticles reconstituted from low density lipoprotein components for delivery of siRNA.

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  • 1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.

Abstract

Cationic solid lipid nanoparticles (SLN), reconstituted from natural components of protein-free low-density lipoprotein, were used to deliver small interfering RNA (siRNA). The cationic SLN was prepared using a modified solvent-emulsification method. The composition was 45% (w/w) cholesteryl ester, 3% (w/w) triglyceride, 10% (w/w) cholesterol, 14% (w/w) dioleoylphosphatidylethanolamine (DOPE), and 28% (w/w) 3beta-[ N-(N',N'-dimethylaminoethane)carbamoyl]-cholesterol (DC-chol). The SLN had a mean diameter of 117+/-12 nm and a surface zeta potential value of +41.76+/-2.63 mV. A reducible conjugate of siRNA and polyethylene glycol (PEG) (siRNA-PEG) was anchored onto the surface of SLN via electrostatic interactions, resulting in stable complexes in buffer solution and in even 10% serum. Under an optimal weight ratio of DC-chol of SLN and siRNA-PEG conjugate, the complexes exhibited higher gene silencing efficiency of GFP and VEGF than that of polyethylenimine (PEI) 25K with showing much reduced cell cytotoxicity. Flow cytometry results also showed that siRNA-PEG/SLN complexes were efficiently taken up by cells. Surface-modified and reconstituted protein-free LDL mimicking SLN could be utilized as noncytotoxic, serum-stable, and highly effective carriers for delivery of siRNA.

[PubMed - indexed for MEDLINE]
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