Title: Interfacial engineering of pyridinium amphiphiles in self-assembled gene delivery systems

 

Abstract: Pyridinium amphiphiles possess a soft charge and can be designed to have a high charge/mass ratio and a high molecular flexibility – all key parameters that recommend their use in synthetic gene delivery systems with in vitro and in vivo efficiency. The presentation will show our recent results towards generating DNA delivery systems with enhanced transfection efficiency and low cytotoxicity through interfacial engineering of pyridinium gemini surfactants and lipids at the level of linker, hydrophobic chains and counterions. The self-assembling of these amphiphiles and the physicochemical properties of the resultant supra-molecular assemblies with and without nucleic acids were studied in bulk and in solution through a combination of techniques that included DSC, X-ray diffraction, polarized microscopy, CMC, dynamic light scattering and zeta potential measurements. The impact of different structural elements and formulation parameters of these pyridinium amphiphiles on their DNA compaction properties, transfection efficiency, and cytotoxicity was assessed simultaneously, which allowed us to establish structure-property and structure-activity relationship correlations within this class of amphiphilic compounds.