Domínguez Arca, VicenteSabín Fernández, Juan DanielGarcía Río, LuisBastos, MargaridaTaboada Antelo, PabloBarbosa Fernández, SilviaPrieto Estévez, Gerardo2022-11-222022-11-222022Journal of Molecular Liquids 366 (2022) 120230http://hdl.handle.net/10347/29452A novel formulation of cationic liposomes was studied by mixing dipalmitoylphosphatidylcholine (DPPC) with tetradecyltrimethylammonium bromide gemini surfactants with different alkane spacer groups lengths attached to their ammonium head-groups. The physicochemical characterization of the cationic liposomes was obtained by combining experimental results from differential scanning microcalorimetry (DSC) with molecular dynamic simulations, in order to understand their structural configuration. An adapted Ising model was used to interpret the results in terms of cooperativity of the phase transitions. The gemini surfactants partition into the lipid bilayer of DPPC liposomes, and the induced changes in colloidal stability and phase transition were analyzed in detail. The DPPC liposomes became positively charged upon gemini surfactant partition, showing increased colloidal stability. Our results show significant differences in structural configuration between gemini surfactants with short and long spacer lengths. While gemini with shorter spacers allocate within the lipid bilayer with both headgroups in the same layer, geminis with longer spacers unexpectedly intercalate in the lipid membrane in a particular zig-zag configuration, with each headgroup located at a different side of the bilayer, altering the coupling degree parameters of the membrane’s phase transition. The extraordinary increase of colloidal stability of DPPC liposomes with gemini surfactants at very low molar ratio and the possibility to tune the physicochemical properties of the membrane by control de spacer length of the geminis opens new possibilities for cationic liposomal formulations with potential applications in vaccines, drug/gene delivery or biosensingeng2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Gemini surfactantsCationic liposomesTrans-gauche isomerizationLambda transitionsLipid-surfactant interactionsjournal article10.1016/j.molliq.2022.1202300167-7322open access