Nanomaterials for transdermal drug delivery: beyond the state of the art of liposomal structures.

A wide range of biomedical materials have been proposed to meet the different needs for controlled oral or intravenous drug delivery. The advantages of oral delivery such as self-administration of a pre-determined drug dose at defined time intervals makes it the most convenient means for the delivery of small molecular drugs. It fails however to delivery therapeutic macromolecules due to rapid degradation in the stomach and size-limited transport across the epithelium. The primary mode of administration of macromolecules is presently via injection. This administration mode is not without limitations, as the invasive nature of injections elicits pain and decreases patients' compliance. Alternative routes for drug delivery have been looked for, one being the skin. Delivery of drugs via the skin is based on the therapeutics penetrating the stratum corneum (SC) with the advantage of overcoming first-pass metabolism of drugs, to deliver drugs with a short-half-life time more easily and to eliminate frequent administrations to maintain constant drug delivery. The transdermal market still remains limited to a narrow range of drugs. The low permeability of the SC to water-soluble and macromolecular drugs poses significant challenges to transdermal administration via passive diffusion through the skin, as is the case for all topically administered drug formulations intended to bring the therapeutic into the general circulation. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to the integration of skin enhancers into pharmaceutical formulations, nanoparticles based on lipid carriers have been widely considered and reviewed. While being briefly reviewed here, the main focus of this article is on current advancements using polymeric and metallic nanoparticles. Next to these passive technologies, the handful of active technologies for local and systemic transdermal drug delivery will be discussed and put into perspective. While passive approaches dominate the literature and the transdermal market, active delivery based on microneedles or iontophoresis approaches have shown great promise for transdermal drug delivery and have entered the market, in the last decade. This review gives an overall idea of the current activities in this field.