Transethosomes Based Nano-interventions For Drug Delivery: Mechanistic Insights, Recent Innovations and Patent Perspectives

Abstract

Transethosomes represent an innovative drug delivery system that integrates the ultra-deformable architecture of transferosomes with the permeation-enhancing attributes of ethosomes. Due to their unique structure, transethosomes display greater skin penetration characteristics than conventional liposomes. These carriers achieve superior penetration through ethanolinduced stratum corneum lipid fluidization and surfactant-mediated elasticity, outperforming liposomes with 3-fold higher deformability, 2-4-fold enhanced flux, and prolonged zero-order release, while remaining intact through skin pores 5-10 times smaller than the vesicle diameter. A systematic literature search was conducted using PubMed, Scopus, Web of Science, Google Scholar, ScienceDirect, and Springer to identify relevant studies published in recent years. The search strategy employed combinations of keywords including transethosomes, ethosomes, transferosomes, elastic lipid vesicles, ethanolic vesicles, topical delivery, transdermal drug delivery, nanocarriers, skin permeation, drug delivery systems, and nanomedicine. Patent information was retrieved from Google Patents, WIPO PATENTSCOPE, Enpacenet, USPTO, CNIPA, and InPASS using similar search terms. Original research publications, review papers, patents, Ph.D. Dissertations, and regulatory publications written in English were included. The study includes a comprehensive characterization of transethosomes, including vesicle morphology, vesicle size, zeta potential, entrapment efficiency, differential scanning calorimetry for thermal behavior, and ex vivo skin permeation. The enhanced drug delivery associated with transethosomes is confirmed through confocal laser scanning microscopy (CLSM) studies of drug distribution. In addition to the above-mentioned characterization, the review also addresses the advantages and disadvantages of transethosomes, different preparation techniques, and the underlying mechanisms of skin penetration. This review covers the application of transethosomes across various routes, including transdermal, topical, ocular, and nasal. It emphasizes their potential for use in clinics upon appropriate modification and functionalization, and points to emerging patents related to transethosomal technologies, indicating growing interest in their clinical and commercial translation. However, clinical progress has been made in formulation development and patent generation; future clinical translation of these products will require scale-up optimizations, ligand functionalization, and standardized trials to confirm their superiority over existing marketed formulations.