Gelation of ethosome-like catanionic vesicles by water-soluble polymers: ethanol and cholesterol effects

Abstract

Ethosome-like catanionic vesicles are vesicular carriers prepared by using ion-pair amphiphiles (IPAs) and relatively high concentrations of ethanol through a semispontaneous process for dermal drug delivery. In this work, the effects of ethanol and cholesterol on the polymer configuration and vesicular membrane rigidity (or hydrophobicity) and therefore the gelation of the as-prepared ethosome-like catanionic vesicles by water-soluble polycations with and without hydrophobic modification (HMP⁺ and P⁺), respectively, were systematically studied for the decyltrimethylammonium-dodecylsulfate (DeTMA-DS) IPA system. The experimental results revealed that the configuration of the polymer chain in aqueous ethanol solution may vary significantly with the dielectric constant of mixed solvents. Moreover, while the vesicular membrane rigidity of the ethosome-like catanionic vesicle was slightly deteriorated by ethanol, it was greatly enhanced by cholesterol. Phase maps and rheological properties of the mixtures of ethosome-like catanionic vesicles and polymers indicated that the interaction between vesicles and polymer HMP⁺ decreases and increases with the increasing ethanol concentration and cholesterol content, respectively. Both ethanol concentration and cholesterol content, however, showed little effect on the interaction between vesicles and polymer P⁺. These findings lead to the conclusion that the gelation of ethosome-like catanionic vesicles by polymer molecules is driven by the hydrophobic more than the electrostatic interactions. Possible mechanisms of ethanol and cholesterol effects on gelation of the ethosome-like catanionic vesicles by the polycations were also proposed based on the experimental results.