Ethosomes As Advanced Transdermal Drug Carriers: A Critical Review of Design, Skin Permeation Mechanisms, Formulation Parameters, and Therapeutic Efficacy

Transdermal drug delivery systems (TDDS) provide an effective route for administering therapeutic agents through the skin into systemic circulation, offering advantages such as improved patient compliance, avoidance of first pass metabolism, and sustained drug release. However, the major challenge limiting their efficiency is the skin’s outermost layer, the stratum corneum, which acts as a strong barrier to drug permeation. Conventional formulations often fail to achieve sufficient bioavailability for many drugs, particularly hydrophilic and large molecular weight compounds. In recent years, vesicular drug delivery systems have gained prominence as advanced carriers for enhancing skin permeation. Among these, ethosomes have emerged as a promising nanocarrier system due to their soft, flexible vesicular structure composed of phospholipids, ethanol, and water. Ethosomes are distinguished by their high ethanol content, which imparts malleability to vesicles and disrupts lipid packing in the stratum corneum, leading to increased drug permeation and deposition within deeper skin layers.The unique composition and mechanism of ethosomes allow for the efficient delivery of both hydrophilic and lipophilic drugs, improving therapeutic efficacy while minimizing side effects. This review critically discusses the design aspects, formulation parameters, and mechanisms underlying ethosomal skin permeation. It also explores the broad therapeutic applications of ethosomes, emphasizing their superiority over conventional transdermal systems. Overall, ethosomes represent a breakthrough in nanocarrier-mediated transdermal delivery, paving the way for more effective, patient-friendly therapeutic approaches.