Dicationic Alkylammonium Bromide Gemini Surfactants. Membrane Perturbation and Skin Irritation

Abstract

Dicationic alkylammonium bromide gemini surfactants represent a class of amphiphiles potentially effective as skin permeation enhancers. However, only a limited number of studies has been dedicated to the evaluation of the respective cytotoxicity, and none directed to skin irritation endpoints. Supported on a cell viability study, the cytotoxicity of gemini surfactants of variable tail and spacer length was assessed. For this purpose, keratinocyte cells from human skin (NCTC 2544 cell line), frequently used as a model for skin irritation, were employed. The impact of the different gemini surfactants on the permeability and morphology of model vesicles was additionally investigated by measuring the leakage of calcein fluorescent dye and analyzing the NMR spectra of 31P, respectively. Detail on the interaction of gemini molecules with model membranes was also provided by a systematic differential scanning calorimetry (DSC) and molecular dynamics (MD) simulation. An irreversible impact on the viability of the NCTC 2544 cell line was observed for gemini concentrations higher than 25 mM, while no cytotoxicity was found for any of the surfactants in a concentration range up to 10 mM. A higher cytotoxicity was also found for gemini surfactants presenting longer spacer and shorter tails. The same trend was obtained in the calorimetric and permeability studies, with the gemini of longest spacer promoting the highest degree of membrane destabilization. Additional structural and dynamical characterization of the various systems, obtained by 31P NMR and MD, provide some insight on the relationship between the architecture of gemini surfactants and the respective perturbation mechanism.

Structure and Conformational Dynamics of DMPC/Dicationic Surfactant and DMPC/Dicationic Surfactant/DNA Systems

“…The temperature changes related to the incorporation of DNA and surfactant molecules into the lamellar phase have been observed for other systems of this type [46]. …”

Synthesis of Gemini Surfactants and Evaluation of Their Interfacial and Cytotoxic Properties: Exploring the Multifunctionality of Serine as Headgroup

“…Moreover, it is noticeable that an increase in chain length from 12 to 16 C atoms promotes a parallel TC 50 decrease (Table 3 and Figure 6). [36] At 4 and 24 h of incubation, the C18 surfactant shows lower cytotoxicity (higher TC 50 ) than the C16 one. [36] At 4 and 24 h of incubation, the C18 surfactant shows lower cytotoxicity (higher TC 50 ) than the C16 one.…”

“…If it is assumed that longer hydrocarbon chains endow surfactants with higher hydrophobicities and, therefore, enhanced propensities to incorporate into the lipid bilayers of cell membranes, greater disturbwww.eurjoc.org ance of membrane-mediated physiological processes would be expected from those surfactants, resulting in more severe toxic outcomes for the cells. [36] At 4 and 24 h of incubation, the C18 surfactant shows lower cytotoxicity (higher TC 50 ) than the C16 one. The cutoff effect is a well-known effect for series of alcohols with increasing chain length.…”

The formation of host–guest complexes between surfactants and cyclodextrins

“…The ability of geminis to make organic compounds soluble in water makes them useful for applications in different fields such as drug formulations [272] and waste water treatment [231]. Other interesting and promising applications involve skin care [273], gene delivery vectors [274,275], antimicrobial effect [276], skin permeation enhancers [277], analytical methods [278,279], and synthesis of gold nanoparticles with tunable longitudinal surface plasmon resonance [280,281].…”