This work aims at understanding the ethanol effects on the gelation behavior of ethosomes with the consideration of encapsulating a hydrophobic material. Gelation of the empty ethosomes by positively charged water-soluble polymers with and without hydrophobic modification, respectively, was systematically studied first for the effects of solution dielectric constant and gelator concentration on the phase map and rheological property of the mixtures. A comparison of the gelation behavior of empty and α-tocopherol acetate (α-TA)-encapsulated ethosomes sheds light on the possible influence of encapsulated hydrophobic material itself on the interaction between ethosomal lipid bilayers and gelator molecules. The experimental results revealed that ethosomes with an optimized amount of ethanol could result in a reasonable lifetime and encapsulation efficiency of more than 90 %. This is due to the effects of the solution dielectric constant on the formability of liposome and the partition of the hydrophobic material (α-TA) between ethosomal lipid bilayer and bulk phase. Moreover, the phase map and rheological property of the ethosome/polymer mixtures were found to be affected by the configuration of the polymer chain in aqueous ethanol solution. That is, the driving interactions between ethosomal lipid bilayers and gelator molecules were dominated by the hydrophobic material more than the electrostatic association. Finally, inclusion of a hydrophobic material, such as α-TA, in the ethosomes had less influence on the gelation behavior of the ethosomes with water-soluble polymers.
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