1-2-oleoylphosphatidylcholine and didodecyldimethylammonium

Cationic amphiphile DDAB (dimethyl-dioctadecyl-ammonium-bromide) can spontaneously form water-dispersed and solid supported mimicking biomembrane structures as well as valuable DNA delivery vehicles whose shape, stability and transfection efficiency can be easily optimized on varying temperature, water content and chemical composition. In this framework, disclosing the thermotropic behavior of DDAB assemblies can be considered as an essential step in conceiving and developing new non-viral vector systems. Our work has been focused primarily on understanding the mesophase structure of silicon supported DDAB thin film on varying temperature at constant relative humidity by energy dispersive X-ray diffraction (EDXD). Diffraction results have then been employed in providing a more comprehensive dynamic light scattering (DLS) analysis of corresponding thermotropic water dispersed vesicles made up of DDAB alone and in combination with helper lecithin DOPC (1,2-dioleoyl-sn-glycero-3-phosphatidylcholine) liposomes. We found that above 55 °C silicon-supported DDAB films undergo a significant thinning effect, whilst DDAB-water vesicles exhibit a reduction in size polydispersity. Upon cooling to 25 °C a distinct silicon supported DDAB mesophase, exhibiting a relative humidity-dependent spacing, has been pointed out, and modeled in terms of a lyotropic metastable gel-crystalline phase.DDAB/DOPC-water vesicles show a temperature-dependent switching in size distribution, leading to promising biomedical applications.

Topics: Humidity; Light; Membranes, Artificial; Molecular Structure; Phosphatidylcholines; Quaternary Ammonium Compounds; Scattering, Radiation; Silicon; Surface-Active Agents; Temperature; Water; X-Ray Diffraction

A vaccine strategy directed to increase Th1 cellular immune responses, particularly to hepatitis C virus (HCV) nonstructural protein 3 (NS3), has considerable potential to overcome the infection with HCV. DNA vaccination can induce both humoral and cellular immune responses, but it became apparent that the cellular uptake of naked DNA injected into muscle was not very efficient, as much of the DNA is degraded by interstitial nucleases before it reaches the nucleus for transcription. In this paper, cationic liposomes composed of different cationic lipids, such as dimethyl-dioctadecylammonium bromide (DDAB), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), or 1,2-dioleoyl-sn-glycerol-3-ethylphosphocholine (DOEPC), were used to improve DNA immunization in mice, and their efficiencies were compared. It was found that cationic liposome-mediated DNA immunization induced stronger HCV NS3-specific immune responses than immunization with naked DNA alone. Cationic liposomes composed of DDAB and equimolar of a neutral lipid, egg yolk phosphatidylcholine (EPC), induced the strongest antigen-specific Th1 type immune responses among the cationic liposome investigated, whereas the liposomes composed of 2 cationic lipids, DDAB and DOEPC, induced an antigen-specific Th2 type immune response. All cationic liposomes used in this study triggered high-level, nonspecific IL-12 production in mice, a feature important for the development of maximum Th1 immune responses. In conclusion, the cationic liposome-mediated gene delivery is a viable HCV vaccine strategy that should be further tested in the chimpanzee model.

Topics: Animals; Antibody Formation; Capsules; Cations; CD4-Positive T-Lymphocytes; Cell Line; Fatty Acids, Monounsaturated; Gene Transfer Techniques; Immunization; Interleukin-12; Liposomes; Mice; Phosphatidylcholines; Plasmids; Quaternary Ammonium Compounds; Th1 Cells; Transfection; Vaccines, DNA; Viral Nonstructural Proteins