Synthesis and characterization of a series of carbamate-linked cationic lipids for gene delivery.

A series of pH-sensitive lipids, la-h [(2,3-bis-alkylcarbamoyloxy-propyl)-trialkylammonium halide] and 2a-d (1-di-methylamino-2,3-bis-alkylcarbamoyloxy-propane), with carbamate linkages between the hydrocarbon chains and an ammonium or tertiary amine head, were synthesized for liposome-mediated gene delivery. The variable length of the carbon chains and the quaternary ammonium or neutral tertiary amine heads allowed us to identify the structure-function relationship showing how these factors would affect cationic lipids in gene delivery performance.