Development of novel diolein-niosomes for cutaneous delivery of tretinoin: Influence of formulation and in vitro assessment

This work describes innovative niosomes, composed of diolein alone or in association with the hydrophilic penetration enhancer Labrasol®, as carriers for cutaneous drug delivery. The model drug was tretinoin and conventional, and Labrasol® containing liposomes was used as controls to evaluate the influence of vesicle composition and the role of Labrasol® on vesicle physico-chemical properties and performance as skin delivery system. Vesicles, prepared by the thin film hydration technique, were characterized in terms of size distribution, morphology, zeta potential, structure, incorporation efficiency, and rheological properties. The influence of carrier composition on tretinoin delivery to human skin was evaluated by in vitro percutaneous experiments, while formulation distribution on human skin and cellular uptake in human keratinocytes were studied using confocal laser scanning microscopy. Result showed that tretinoin loaded diolein-niosomes formed unilamellar vesicles very similar in physico-chemical properties to liposomes. The role of Labrasol® was similar in niosomes and liposomes. Its addition affected vesicle structure and size, by formation of an interdigitate bilayer with higher curvature and larger vesicle size, and rheological properties. Indeed, the presence of Labrasol® allowed both niosomes and liposomes to shift from Newtonian to pseudo-plastic behavior. Confocal laser microscopy highlighted an important contemporaneous deposition of hydrophilic and lipophilic vesicle components in stratum corneum and a high vesicle affinity for skin appendages when Labrasol® was added to the diolein-niosomes. Moreover, all samples were internalized in human keratinocytes in vitro.