NANOVECTORS FOR TRANSDERMAL ADMINISTRATION: WHERE ARE WE?

The skin is the most important barrier of human body to prevent the absorption of exogenous substances. Its ability to limit the absorption of exogenous substances is exercised by the most superficial layer of the epidermis, the stratum corneum, which consists of about 15-20 layers of corneocytes supported by keratin fibres. The extracellular spaces are filled with a very dense lipid matrix organized in periodic lamellae, whereas the interlamellar spaces are constituted by a more fluid lipid matrix. In addition, where the corneocytes are not perfectly overlapped, pores with a higher water content are created. This complex organization allows only the passive diffusion of small molecules with peculiar chemical-physical properties. In all the other cases, it is necessary to improve the transdermal absorption of drugs using techniques able to alter reversibly the functionality of the stratum corneum, such as chemical skin penetration enhancers, iontophoresis or sonophoresis. In the era of nanotechnology, an intense effort has been made to design nanocarriers able to permeate the skin (e.g., polymeric nanoparticles, metal or solid-lipid, micro- and nanoemulsions, lipid vesicles). Nevertheless, the results are contradictory and there is scepticism in the scientific community about the real benefits of these systems compared to other traditional approaches. In fact, assuming the stratum corneum as a nanoporous membrane with openings of about 20-40 nm, the size of most of the nanocarriers is too big for permitting theoretically the skin penetration and diffusion. However, despite this consideration, on the market there are some medicinal products consisting of lipid vesicles. Starting from the critical analysis of the published information on possible permeation mechanisms of different types of nanocarriers, this review outlines lights and shadows on the (trans-)dermal administration of these drug delivery systems.