Varsha A A

Transdermal drug delivery systems (TDDS) is a promising method of non-invasive delivery of drug molecules, and it has the following benefits: it avoids first-pass metabolism, minimizes intestinal breakdown and increases patient compliance. The stratum corneum however presents a great obstacle to drug permeation and more so on hydrophilic and high-molecular-weight drugs. More recent developments have then been directed at the inclusion of chemical permeation enhancers (CPEs) which comprise alcohols, fatty acids, terpenes and surfactants that disturb the structure of the lipids, and increases the solubility of the drug in order to enhance permeation. Simultaneously, the so-called microneedle (MN) technologies, which could be solid, coated, hollow, or dissolving, have been developed to generate the temporary microchannels in the skin and allow deep and efficient drug delivery with low discomfort and minimal damage. Effectiveness, safety, and mechanism of both CPEs and MNs were proven in preclinical trials based on rodent and porcine models, where porcine skin was also compared as a translational-friendly model known to mimic the human one. Noteworthy, the formulation of CPEs with microneedles has demonstrated the synergetic phenomenon, by improving the drug flux, extending therapeutic potential, and extending the ability to deliver a broadened range of molecules such as peptides, hormones, and even vaccines. This review summarizes the existing evidence and points at the translational prospects of the above-mentioned technologies, as well as the future directions of clinical application and improvement of formulation in trans-dermal therapies.