Characterization of a pH-sensitive surfactant, dodecyl-2-(1′-imidazolyl) propionate (DIP), and preliminary studies in liposome mediated gene transfer

The inefficiency of non-viral gene delivery systems, relative to viral systems, is likely due, in part, to the failure of endosomes to release DNA before reaching degradative lysosomes. A solution is to incorporate compounds in a delivery vector that will selectively increase the release of endosomally encapsulated DNA. To meet the above criteria, we designed, synthesized, and characterized the physicochemical and biological properties of such a compound, dodecyl-2-(1'-imidazolyl) propionate (DIP) to enhance cationic liposome mediated gene delivery. Several surface active techniques were used to characterize DIP lysing membranes. The critical micelle concentration of DIP was between 0.10-0.18 mM and the effective release and solubilization ratios were 1.0 and 4.0, respectively. DTP facilitated membrane disruption in both a pH and concentration dependent manner. In the presence of esterase at pH 7.0, the hydrolysis rate increased 32-fold indicating DIP can be degraded in the biological milieu. Toxicity of DIP by MTT assay in the SKnSK cell line demonstrated an ID50 of 1.2 mM, which is 30-fold higher than the concentration of DIP used to enhance gene transfection. When incorporated into cationic-liposomes, DIP enhanced transgene expression in vitro by 5-fold. The results of the study indicate that DIP may be a useful adjuvant to increase non-viral gene delivery to cells. (C) 1998 Elsevier Science B.V.