Distal Cationic Poly(Ethylene Glycol) Lipid Conjugates in Large Unilamellar Vesicles Prepared by Extrusion Enhance Liposomal Cellular Uptake

Cationic poly(ethylene glycol)‐lipid conjugates (CPLs), a class of lipid designed to enhance the interaction of liposomes with cells, possess the following architectural features: 1) a hydrophobic lipid anchor of distearoylphosphatidylethanolamine (DSPE); 2) a hydrophilic spacer of poly(ethylene glycol); and 3) a cationic head group prepared with 0, 1, 3, or 7 lysine residues located at the distal end of the PEG chain, giving rise to CPL possessing 1, 2, 4, or 8 positive charges, respectively (CPL1 to CPL8). Previously we have described the synthesis of CPL, have characterized the postinsertion of CPL into PEG‐containing LUVs and SPLP (stabilized plasmid‐lipid particles), have shown significant increases in the binding of CPL‐LUV to cells, and have observed dramatically enhanced transfection (up to a million‐fold) of cells with CPL‐SPLP in the presence of calcium [Chen et al. (2000) Bioconjugate Chem. 11, 433–437; Fenske et al. (2001) Biochim. Biophys. Acta 1512, 259–272; Palmer et al. (2003) Biochim. Bio...