Microneedles as transdermal delivery systems: combination with other enhancing strategies

Transdermal drug delivery has exhaustively been studied over the past decades due to its multiple advantages over other administration routes; however, drugs that can be administered by this via are few owe to the stratum corneum permeability properties. Recently, several strategies to bypass the upper-layer skin barrier have been developed. One of the latest advances in this area has been the use of micro-scale needles, which painlessly pierce skin, increasing the passage of drugs with unfavourable skin permeability (i.e., low potent, hydrophilic, high molecular drugs) by several orders of magnitude, by bypassing the stratum corneum. Microneedles have shown to be safe and easy-to-use for drug administration, a nouvelle alternative to hypodermic needle injections, and an array in which drugs can be included to attain a controlled release as to achieve a higher drug delivery. Several works have demonstrated that such devices dramatically increase transdermal delivery of large molecules, thus nowadays microneedles have been regarded as a potential technology approach to be employed alone or with other enhancing methods such as electroporation and iontophoresis, as well as with different drug carriers (e.g., lipid vesicles, micro- and nanoparticles). Hence, this review is mainly focused on presenting the results obtained when combining microneedles with a variety of strategies to ease drug diffusion through skin, including physical enhancers and drug carrier systems.