Ultra-deformable transethosomal vesicle for enhancing transdermal delivery of NSAIDs: a comprehensive review

Topical and transdermal drug delivery methods provide an enticing option to conventional oral administration of non-steroidal anti-inflammatory medications (NSAIDs) by diminishing gastrointestinal complications and bypassing hepatic first-pass metabolism. However, the therapeutic performance of topical NSAID formulations is commonly restricted by the barrier characteristics of the stratum corneum, causing poor drug diffusion and suboptimal concentrations at the desired region. Transethosomes, a cutting-edge generation of ultra-deformable lipid vesicles formed from phospholipids, ethanol, and edge activators, have shown as viable nanocarriers for mitigating these limits. The improved pliability, compact vesicle size, and remarkable skin-penetration capacity support the effective transfer of encapsulated medicines through the skin, culminating in better bioavailability and therapeutic benefits. This review thoroughly outlines the composition, physicochemical characteristics, mechanisms of skin permeation, methods of preparation, and characterization techniques of transethosomal vesicles. Special attention is directed towards their use in the transdermal delivery of NSAIDs, underscoring results from preclinical studies that reveal improved skin permeation, greater drug retention, prolonged drug release, and enhanced anti-inflammatory effectiveness. Current challenges, such as formulation stability, large-scale manufacturing, and clinical translation, are thoroughly examined. Transethosomal vesicles serve as a versatile and promising platform for improving transdermal delivery of NSAIDs, potentially playing a significant role in the advancement of safer and more effective therapeutic strategies for inflammatory disorders.