Structure-activity investigation on the gene transfection properties of cardiolipin mimicking gemini lipid analogues

Abstract

A structure-activity relationship has been explored on the gene transfection efficiencies of cardiolipin mimicking gemini lipid analogues upon variation of length and hydrophilicity of the spacer between the cationic ammonium headgroups and lipid hydrocarbon chain lengths. All the gemini lipids were found to be highly superior in gene transfer abilities as compared to their monomeric lipid and a related commercially available formulation. Pseudoglyceryl gemini lipids bearing an oxyethylene (-CH₂-(CH₂-O-CH₂)_m-CH₂-) spacer were found to be superior gene transfecting agents as compared to those bearing polymethylene (-CH₂)_m-) spacers. The major characteristic feature of the present set of gemini lipids is their serum compatibility, which is most often the major hurdle in liposome-mediated gene delivery.