Chemical–physical properties and cytotoxicity of N-decanoyl amino acid-based surfactants: Effect of polar heads

[Display omitted] •N-Decanoyl aminoacyl derivates were analyzed at physiological pH in comparison to SDS.•Toxicological profile was assessed by MTT, LDH, hemolytic assays and TEER tests.•N-Decanoyl surfactants were less toxic than SDS in tested cell lines and erythrocytes.•Hydrophilic interactions amphiphiles/cell membranes determined cellular toxicity.•Polar heads affect the aggregation state and cell toxicity profiles. N-acyl amino acids-based surfactants are an attractive class of anionic amphiphiles alternative to sulphate-based surfactants, potentially employed as excipients for pharmaceutical applications in which an anionic surfactant is needed. Thus, a systematic characterization of their toxicological profile is required, particularly in comparison to sodium dodecyl sulphate (SDS), a widely employed surfactant in pharmaceutical formulations. This work reported a systematic study on the relationship between the structures of N-acyl amino acids-based surfactants, their physicochemical properties and toxicological profiles. N-Decanoyl aminoacids with different polar heads (leucine, methionine, serine and proline) were synthesized and characterized in terms of surface tension and aggregation properties. Different human cell lines (Caco-2, A549, Calu-3) and erythrocytes were selected as model for oral, respiratory or parenteral administration to evaluate surfactants cytotoxicity. Moreover, the ability of surfactants to interact with cell membranes was assessed by the Trans Epithelial Electrical Resistance (TEER). Results suggested that the different polar heads affect the aggregation state and cell toxicity profiles of surfactants, but not their surface properties. According to the toxicity assays, all N-decanoyl surfactants were less toxic than SDS, suggesting that hydrophilic interactions between amphiphiles and cell membranes play a key role in determining cellular toxicity.