Dicephalic ionic surfactants in fabrication of biocompatible nanoemulsions: Factors influencing droplet size and stability

The present work has been carried out to explore the potential of two novel ionic dicephalic-type surfactants, i.e., positively charged N,N-bis[3,3′-(trimethylammonio)propyl]-dodecanamide dimethylsulphate, C12(TAPAMS)2 and anionic disodium N-dodecyliminodiacetate, C12(COONa)2 for spontaneous formation of biocompatible and stable oil-in-water (o/w) nanoemulsions. Initially, we examined ternary phase diagrams of surfactant–oil–water (SOW) systems containing different ratios of C12(TAPAMS)2 or C12(COONa)2 as the surfactant entity (S), oleic acid, isopropyl palmitate or isopropyl myristate as the oil phase (O) and the water phase (W) by the titration method. Then, all obtained nanoemulsions were characterized by visual and microscopic observations, as well as dynamic light scattering (DLS) measurements of particle sizes and size distributions. Results of cryo-TEM and DLS showed that the studied droplets making up the nanoemulsions have a nearly monodisperse size distribution (DH < 100 nm, PdI < 0.2). Backscattered profiles obtained by the turbidimetric technique proved high kinetic stability of the obtained systems whereas Doppler electrophoresis revealed their large positive or negative ζ-potential. In order to test the nanoemulsions biocompatibility under the surfactants concentration, cytotoxicity of the optimized formulations was evaluated in vitro upon two normal human skin cell lines, i.e., cutaneous keratinocytes (HaCaT) and gingival fibroblasts (HGF). The analyzed parameters – oil composition, surfactant type, and surfactant-to-oil ratio – were all found to influence the droplet size, charge and stability of the systems produced. Our results prove that the studied nanoemulsions, stabilized by dicephalic ionic surfactants, may provide new biocompatible colloidal systems, designated mainly for cosmetics, personal and household care products.