Ethosome-Based Colloidal Systems for Transdermal Delivery: The Role of Biosurfactant in Enhancing Stability and Efficacy

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 (D<i>_h</i>). The effects of phospholipid concentration and homogenization were also assessed. SEM imaging confirmed the spherical morphology of vesicles. The optimal formulation comprised 30% (<i>w</i>/<i>w</i>) ethanol, 2.5% (<i>w</i>/<i>w</i>) phospholipid, 10% (<i>w</i>/<i>w</i>) ethylene glycol, and 1.25% (<i>w</i>/<i>w</i>) Tween 80. A comparable mixed-surfactant system (0.625% <i>w</i>/<i>w</i>; 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 D<i>_h</i> 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.