Development of ethosome-like catanionic vesicles for dermal drug delivery

A carrier for enhanced skin delivery of drugs has ever been discovered and named “ethosomes,” which are phospholipid vesicular systems embodying ethanol in relatively high concentrations. This work aims at developing competent ethosome-like catanionic vesicles for dermal drug delivery. The preparation of double-chained catanionic surfactant (or ion-pair-amphiphile, IPA) DeTMA-DS from single-chained cationic surfactant (decyltrimethylammonium bromide, DeTMAB) and anionic surfactant (sodium dodecyl sulfate, SDS) by the precipitation method was demonstrated first. This lipid-like surfactant was thereafter used as the material to prepare the catanionic vesicles with the aid of ethanol as the cosolvent in aqueous buffer solution by a simple semispontaneous process. Formability and physical stability of the as-prepared catanionic vesicles were discussed based on the viewpoint of mixed solvent dielectric constant. The potential application of the catanionic vesicles as nano-carriers in dermal drug delivery was demonstrated by the encapsulation of vitamin E acetate (α-tocopherol acetate, α-TA). Furthermore, effects of cholesterol addition on physical stability, bilayer membrane rigidity, and encapsulation efficiency of the catanionic vesicles with 20% ethanol, in which the most stable vesicle can be formed, was systematically studied. The experimental results revealed that vesicle stability can be enhanced further by the addition of cholesterol. The vesicle membrane rigidity and encapsulation efficiency are both increased with the increase of cholesterol addition. It is, therefore, suggested that the encapsulation efficiency of α-TA in the catanionic vesicles is dependent on the vesicle membrane rigidity. Finally, the results of gelation of catanionic vesicles by a water soluble polymer with hydrophobical modification were also reported and the role played by the vesicular bilayer rigidity in the interaction between catanionic vesicles and polymer molecules were discussed. The phase maps and the rheological properties obtained for mixtures of catanionic vesicles and polymer molecules may provide useful information for practical use of the catanionic vesicles in dermal delivery of drugs.

► Successful development of ethosome-like catanionic vesicles for dermal drug delivery was demonstrated.
► Drug encapsulation efficiency was correlated with vesicular bilayer properties.
► Competent drug carrier formulation can be tailored by the concentrations of ethanol and cholesterol.