Ex Vivo Evaluation of Ethosomes and Transethosomes Applied on Human Skin: A Comparative Study

Int J Mol Sci. 2022 Dec 1;23(23):15112. doi: 10.3390/ijms232315112.


In this study, the transdermal fate of vesicular nanosystems was investigated. Particularly, ethosomes based on phosphatidylcholine 0.9% w/w and transethosomes based on phosphatidylcholine 0.9 or 2.7% w/w plus polysorbate 80 0.3% w/w as an edge activator were prepared and characterized. The vesicle mean size, morphology and deformability were influenced by both phosphatidylcholine and polysorbate 80. Indeed, the mean diameters of ethosome were around 200 nm, while transethosome's mean diameters were 146 or 350 nm in the case of phosphatidylcholine 0.9 or 2.7%, w/w, respectively. The highest deformability was achieved by transethosomes based on phosphatidylcholine 0.9%, w/w. The three types of vesicular nanosystems were applied on explanted human skin maintained in a bioreactor. Transmission electron microscopy demonstrated that all vesicles were able to enter the skin, keeping their structural integrity. Notably, the vesicle penetration capability was influenced by their physical-chemical features. Indeed, ethosomes reached keratinocytes and even the dermis, phosphatidylcholine 0.9% transethosomes were found in keratinocytes and phosphatidylcholine 2.7% transethosomes were found only in corneocytes of the outer layer. These findings open interesting perspectives for a differentiated application of these vesicles for transdermal drug delivery as a function of the cutaneous pathology to be addressed.

Keywords: X-ray diffraction; bioreactor; cryogenic transmission electron microscopy; ethosomes; explanted skin; transethosomes; transmission electron microscopy.

MeSH terms

  • Administration, Cutaneous
  • Drug Carriers* / chemistry
  • Humans
  • Liposomes / chemistry
  • Phosphatidylcholines / metabolism
  • Skin / metabolism
  • Skin Absorption*


  • Drug Carriers
  • Phosphatidylcholines
  • Liposomes

Grant support

This research received no external funding.