Skin is composed of a natural barrier protecting the body from external harm such as chemical and micro-organism intrusion, UV exposure and dryness and also from mechanical damage. The skin has a multilayered structure: extending from the external layer into the internal layers, including the stratum corneum (SC) composed of dead keratinized cells, below the epidermis and dermis, and subcutaneous tissue. Among the keratinized cells, there is a lipid matrix composed of ceramides, fatty acids, cholesterol and cholesterol esters, which has a cement-like function to provide excellent barrier properties to the skin [1-3]. When a drug or active ingredient is topically applied on to the skin surface, there are, in theory, three penetration pathways though the skin barrier: (1) the intercellular pathway, (2) the hair follicles and (3) the transcellular pathway. In the first, which is the most well-known pathway, the substance diffuses through the stratum corneum via the lipid layers surrounding the corneocytes. In the second, the hair follicles serve as a relevant pathway because a dense network of blood capillaries supporting efficient penetration surrounds them, and they also act as a ‘reservoir’ of the active compound topically applied on the skin. And third, the less understood pathway is transcellular penetration by the direct transportation of drugs through the lipid layers and corneocytes to the living cells (Fig. 1) [1, 3, 4].