The success of gene therapy as a revolutionary method to treat diseases relies on finding delivery systems that can efficiently transfer and express (transfect) DNA into target cells while producing reduced cytotoxic effects. Recently, pyridinium amphiphiles were shown to generate promising transfection systems that can fulfill these requirements. Within this class of amphiphiles, the pyridinium gemini surfactants, defined as surfactants made up of two identical amphiphiles linked at the level of the polar head by a spacer, proved to be particularly efficient.In the present study we have evaluated the possibility to further enhance the transfection efficiency of these vectors by reengineering their interfacial properties via linker and counterion optimization. Interfacial and self-assembling properties of the novel amphiphiles have been studied in bulk, and in solution. Biological results are showing a dramatic enhancement of the transfection efficiency of the new vectors as compared with their congeners bearing hydrophobic linkers. Transfection activity was found to depend highly on the counterion nature. We will present the complete formulation study, revealing the main factors that are affecting the lipoplex nanoparticles formation and stability. We will also present a detailed structure activity relationship study, emphasizing the impact of each structural element on the aggregation and transfection properties of this novel class of pyridinium amphiphiles.

Dramatic enhancement of transfection efficiency of pyridinium gemini surfactants through interfacial engineering

244th National Meeting (2012)

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