Amphiphilic dicationic surfactants, known as gemini surfactants, are currently studied for gene delivery purposes. The gemini surfactant molecule is composed of two hydrophilic “head” groups attached to hydrophobic chains and connected via molecular linker between them. The influence of different concentrations of 1,5-bis (1-imidazolilo-3- decyloxymethyl) pentane chloride (gemini surfactant) on the thermotropic phase behaviour of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers with and without the presence of DNA was investigated using Fourier transformed infrared (FTIR) and circular dichroism (CD) spectroscopies, small angle scattering of synchrotron radiation and differential scanning calorimetry. With increasing concentration of surfactant in DMPC/DNA systems, a disappearance of pretransition and a decrease in the main phase transition enthalpy and temperature were observed. The increasing intensity of diffraction peaks as a function of surfactant concentration also clearly shows the ability of the surfactant to promote the organisation of lipid bilayers in the multilayer lamellar phase.

Dicationic (also known as gemini or dimeric) bis-alkylimidazolium surfactants belong to a group of non-viral transfection systems proposed for the successful introduction of different types of nucleic acids (i.e., siRNA, DNA oligomers, and plasmid DNA) into living cells.

Dimeric cationic surfactants (gemini-type) are a group of amphiphilic compounds with potential use in gene therapy as effective carriers for nucleic acid transfection (i.e., siRNA, DNA, and plasmid DNA). Our studies have shown the formation of lipoplexes composed of alkanediyl-α,ω-bis[(oxymethyl)dimethyldodecylammonium] chlorides and selected 21-base-pair nucleic acid (dsDNA and siRNA) oligomers. To examine the structure and physicochemical properties of these systems, optical microscopy, circular dichroism spectroscopy (CD), small-angle X-ray scattering of synchrotron radiation (SR-SAXS), and agarose gel electrophoresis (AGE) were used. The lengths of spacer groups of the studied surfactants had a significant influence on the surfactants’ complexing properties. The lowest charge ratio (p/n) at which stable lipoplexes were observed was 1.5 and the most frequently occurring microstructure of these lipoplexes were cubic and micellar phases for dsDNA and siRNA, respectively. The cytotoxicity tests on HeLa cells indicated the non-toxic concentration of surfactants to be at approximately 10 µM. The dicationic gemini surfactants studied form complexes with siRNA and dsDNA oligomers; however, the complexation process is more effective towards siRNA. Therefore these systems could be applied as transfection systems for therapeutic nucleic acids.

No abstract

No abstract