Transethosomes: A Review of Ultra-Deformable Vesicles for Deep Dermal and Transdermal Delivery

The advantages of transdermal drug administration include avoidance of first pass effect, sustained release, and better patient compliance. The major hurdle is the stratum corneum, which does not allow penetration of large molecules as well as hydrophilic molecules, resulting in the lack of suitability of transdermal delivery systems for hydrophilic molecules, macromolecules, and peptides. Several vesicular drug delivery systems such as liposomes, niosomes, ethosomes, and transfersomes have been designed to overcome this problem, but all these systems suffer from certain intrinsic drawbacks. Ethosomes do not penetrate beyond the upper layers of the epidermis, whereas transfersomes tend to aggregate. A new approach in vesicular delivery has resulted in the development of transethosomes, which are a combination of lipid fluidization due to the presence of ethanol along with extreme deformability due to the use of edge activators for achieving deeper skin penetration. This review article will focus on the structure and composition of transethosomes, mechanisms responsible for their high permeation, and major methods used for their preparation, which include thin film hydration, cold, hot, and injection methods. Major characterization parameters are also reviewed along with their formulation evaluation methods. The use of such carriers in therapeutic application areas like antidiabetes, anti-inflammatory, anticancer, antifungal, and CNS active agents delivery are discussed with supportive quantitative results that demonstrate improvement in permeability and efficacy compared to traditional systems. Their strengths and weaknesses have been assessed critically, and the future direction of research in terms of their QbD optimization, stimuli-responsive functionalization, targetable surface modification, and improved long-term stability has been described.