Novel cationic surfactants with cleavable carbamate fragment: Tunable morphological behavior, solubilization of hydrophobic drugs and cellular uptake study

The new cationic surfactants containing octyl and dodecyl carbamate moiety in the head group and hexadecyl tail were synthesized and characterized. They demonstrate versatile self-assembling behavior strongly controlled by structural characteristics of amphiphilic molecules. The octyl derivative at a concentration of 0.06 mM forms micelles, which can undergo structural rearrangement with the increase of surfactant content in the solutions (above 0.01 M). Compound with a dodecyl substituent, upon reaching a critical concentration, forms large aggregates without passing through the micellar stage. Combination of different techniques makes it possible to assume that morphological transitions between micelles and vesicles probably occurs with the variation in structural characteristics and concentration of surfactants. This is supported by dynamic light scattering and transmission electron microscopy, as well as changes in characteristics of spectral probes sensitive to micropolarity and packing parameters of aggregates. Aggregates formed showed high solubilization capacity, exceeding that of typical cationic micelles, toward Orange OT hydrophobic dye and poorly water soluble anti-inflammatory drugs, indomethacin and meloxicam. Carbamate-containing surfactants demonstrated the ability to penetrate through cell membrane, delivering the solubilized hydrophobic substances into the cell, which was testified by flow cytometry and fluorescence microscopy with DAPI and Nile Red dyes.