Thermodynamic and aggregation properties of aza- and imino-substituted gemini surfactants designed for gene delivery

Abstract

Improving the efficiency of gene delivery by using non-viral vectors is currently an area of considerable research interest. Novel derivatives of gemini surfactants having aza- (12-5N-12, 12-7N-12, 12-8N-12) and imino- (12-7NH-12) substituted spacer groups and C12 tails have been designed to improve DNA transfection. Physicochemical characterization of micelle and interfacial properties of these cationic compounds are reported. The effect of these substitutions on the aggregation properties of the gemini surfactants is discussed in the context of results for the 12-s-12 and 12-EOx-12 gemini series, previously reported in the literature. Aza substitution results in a spacer of intermediate hydrophobicity to the above series, reflected by the magnitude of both the critical micelle concentrations and head group areas. Enthalpy and apparent molar volume of micellization data illustrate the differences in the aggregation properties that result from the bulkier and more hydrophobic aza-substituent in the spacer as compared to an ether oxygen (for the 12-EOx-12 series) containing spacer. The 12-7N-12 and 12-8N-12 compounds show aberrant features in the surface tension and enthalpy of dilution results that are not observed for the 12-5N-12 and 12-7NH-12 compounds. Premicelle association is considered to be a source of this behaviour.