title: Characterization of a pH-sensitive surfactant, dodecyl-2-(1'-imidazolyl) propionate (DIP), and preliminary studies in liposome mediated gene transfer.
abstract: 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. DIP 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 SKnSH 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.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville 32610, USA.
authors.forename: E
authors.initials: E
authors.lastname: Liang
authors.forename: J
authors.initials: J
authors.lastname: Hughes
mesh_terms: D005452:Fluoresceins / Q000737:chemistry; D018014:Gene Transfer Techniques; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D008081:Liposomes; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D005452:Fluoresceins; D007093:Imidazoles; D008081:Liposomes; C100541:N-dodecyl-2-imidazole propionate; D013501:Surface-Active Agents; C007740:fluorexon