Jagoda Chudzińska, Agata Wawrzyńczak, Agnieszka Feliczak‐Guzik
The effectiveness of transdermal drug delivery is restricted by the barrier properties of the stratum corneum. Ethosomes, as vesicular carriers, offer a promising approach to enhance dermal bioavailability. This study aimed to optimize ethosome composition and preparation parameters to improve physicochemical stability and performance. The influence of alcohols (ethyl, n-butyl, n-propyl, isopropyl, tert-butyl), glycols (propylene glycol, ethylene glycol, 1,3-butanediol), and surfactants (Tween 80, Mirasoft® SL L60) was systematically investigated. Stability was evaluated through zeta potential (ZP), polydispersity index (PDI), and hydrodynamic diameter (Dh). The effects of phospholipid concentration and homogenization were also assessed. SEM imaging confirmed the spherical morphology of vesicles. The optimal formulation comprised 30% (w/w) ethanol, 2.5% (w/w) phospholipid, 10% (w/w) ethylene glycol, and 1.25% (w/w) Tween 80. A comparable mixed-surfactant system (0.625% w/w; 60% Tween 80 and 40% Mirasoft® SL L60) exhibited similar stability, indicating that glycolipid-based biosurfactants can reduce conventional surfactant requirements. Homogenization significantly enhanced colloidal stability, lowering PDI from 0.366 to 0.083 and Dh from 254 nm to 156 nm, evidencing decreased aggregation and improved size uniformity. Overall, formulation composition and processing conditions critically determine ethosome stability and transdermal delivery efficiency.