Modulation of membrane deformability and stability in liposomes incorporating arginine-based surfactants

This study investigates the ability of two arginine-based surfactants-N^α-benzoyl-arginine decyl- or dodecylamide hydrochloride (Bz-Arg-NHC₁₀ or Bz-Arg-NHC₁₂, respectively)-to act as edge activators (EA) in soy phosphatidylcholine (SPC) liposomes. Liposomes containing 20 mol% of either Bz-Arg-NHC₁₀ or Bz-Arg-NHC₁₂ (SPC20C10 and SPC20C12, respectively), along with surfactant-free controls, were prepared by thin-film hydration and characterized in terms of size, polydispersity index, and Z potential. Vesicle deformability was assessed by extrusion-based assays, while membrane organization and interfacial hydration were evaluated using Laurdan generalized polarization (GP). Lateral packing properties were analyzed through surface pressure-area isotherms of the corresponding lipid monolayers, and storage stability was monitored over 90 days at 4 °C. Both surfactants were incorporated without significantly affecting vesicle size (∼140-145 nm). However, only SPC20C10 exhibited markedly enhanced deformability (D = 6358 % P·min⁻¹), whereas SPC20C12 showed values comparable to control liposomes. Laurdan analysis revealed decreased GP values for both systems, indicating increased interfacial disorder, while a significant reduction in compressibility modulus was observed only for SPC20C10, reflecting disruption of lateral packing. Stability studies showed that SPC20C10 preserved its physicochemical properties for up to 30 days but exhibited reduced long-term stability compared to controls. These results demonstrate that Bz-Arg-NHC₁₀ acts as an effective EA by promoting membrane softening through disruption of lateral packing, whereas Bz-Arg-NHC₁₂ induces interfacial changes without sufficient mechanical modulation. Overall, our work reveals that interfacial disorder is not sufficient to yield ultradeformability; instead, a measurable loss of lateral packing cohesion appears as the key mechanical signature of effective edge activation in SPC membranes.