Understanding Microemulsions and Nanoemulsions in (Trans)Dermal Delivery

Continuously explored in pharmaceuticals, microemulsions and nanoemulsions offer drug delivery opportunities that are too significant to ignore, namely safe delivery of clinically relevant drug doses across biological membranes. Their effectiveness as drug vehicles in mucosal and (trans)dermal delivery is evident from the volume of published literature. Commonly, their ability to enhance skin permeation is attributed to dispersion size, a characteristic closely related to solubilization capacity. However, the literature falls short on distinctions between microemulsions and nanoemulsions for definitions, behavior, or specific differences in their mechanisms of action in (trans)dermal delivery. The focus is typically on surfactant/cosurfactant ratio and droplet size but the role of mesostructures or the effect of cosolvent (C sol ), oil (O) or water (W) on permeation profile remain poorly explained. Towards a deeper understanding of these vehicles in (trans)dermal drug delivery, this review begins with their conceptual and practical distinctions before delving into the published works for less obvious but potentially important underlying mechanisms; notably composition and the competitive positioning of system constituents in the resulting microstructures and subsequent effect(s) these may have on skin structures and drug permeability. For practical purposes, this review focuses on formulation systems based on ternary diagrams with commonly accepted non-ionic surfactants, cosurfactants, cosolvents, and oils used in pharmaceutical applications. Graphical Abstract