ETHOSOMES IN TRANSDERMAL DRUG DELIVERY: FORMULATION STRATEGIES, SKIN-PENETRATION MECHANISMS, CHARACTERIZATION AND RECENT THERAPEUTIC APPLICATIONS

Dipesh Sharma*, Krish Bagla

Transdermal drug delivery systems (TDDS) have emerged as an attractive alternative to conventional oral and parenteral routes because they can provide sustained drug delivery, improve patient compliance, and, for suitable drugs, reduce gastrointestinal degradation and first-pass hepatic metabolism. However, the stratum corneum, the outermost layer of the skin, represents a major barrier to the penetration of most therapeutic molecules. Vesicular nanocarriers have therefore been extensively investigated to improve drug transport across the skin. Ethosomes are deformable phospholipid-based vesicles containing a relatively high concentration of ethanol, which distinguishes them from conventional liposomes. Ethanol modifies the organization and fluidity of skin lipids and contributes to the flexibility of the vesicular membrane, facilitating penetration into deeper skin layers. Ethosomes can accommodate both hydrophilic and lipophilic active pharmaceutical ingredients and have been investigated for topical, dermal and systemic delivery. Their composition generally includes phospholipids, ethanol, water and the drug, while cholesterol, edge activators and other functional excipients may be incorporated depending on the formulation objective. Various preparation techniques, including cold method, hot method, ethanol injection and thin-film hydration, have been reported. Critical quality attributes include vesicle size, polydispersity index, zeta potential, morphology, entrapment efficiency, drug loading, in-vitro release, ex-vivo permeation and stability. Recent research has expanded ethosomal applications into anti-inflammatory, antimicrobial, antifungal, anticancer, cardiovascular, metabolic, neurological and cosmetic delivery. Nevertheless, challenges associated with long-term stability, ethanol concentration, formulation reproducibility, scale-up, skin irritation, regulatory requirements and clinical translation remain. This review discusses the composition, types, preparation methods, mechanism of skin penetration, characterization, advantages, limitations, therapeutic applications and future prospects of ethosomes as advanced transdermal drug delivery carriers.