Pegylated and Non-Pegylated siRNA Lipoplexes Formulated with Cholesteryl Cytofectins Promote Efficient Luciferase Knockdown in HeLa tat luc Cells.

Delivery of small interfering RNAs (siRNAs) remains a major challenge in their development for therapeutic applications, and cationic liposomes are being actively investigated for this purpose. Six liposome formulations containing the cytofectins 3β[N-(N ′,N ′-dimethylaminopropane)-carbamoyl] cholesterol (Chol-T) or 3β[N-(N ′,N ′,-dimethylaminopropylsuccinamidohydrazido)-carbamoyl] cholesterol (MS09) and varying amounts of distearoylphosphatidylethanolamine poly(ethylene glycol)2000, were prepared. Lipoplexes formed with siRNA were characterized by gel retardation analysis and cryo-electron microscopy. All lipoplexes exhibited low cytotoxicity in the HeLa tat luc cell line while Chol-T lipoplexes, containing anti-luciferase siRNA, achieved 93.4% knockdown of the luciferase transcript at 30 nM siRNA. Poly(ethylene glycol)2000incorporation only marginally reduced knockdown efficiency. [ABSTRACT FROM AUTHOR]