Transdermal delivery of peptide and protein drugs: An overview

Recently, a large number of new and potentially potent peptide and protein drugs have been developed. Their systemic delivery is difficult because they are rapidly cleared from the bloodstream, are of large molecular size, are vulnerable to proteolytic attack and tend to undergo aggregation, adsorption and denaturation. Controlled release strategies have many advantages over the current delivery method of injection or intervenous infusion. Controlled release allows for prolonged delivery while maintaining the drug concentration within therapeutic limits. It also improves and increases patient compliance by removing the discomfort of repeated applications. The transdermal route of delivery is particularly attractive because it avoids peptide and protein degradation via the gastrointestinal tract and the hepatic first‐pass effect, and delivery can be interrupted by simply removing the device. Its primary problem is that the skin is an excellent barrier to large, hydrophilic, polar compounds. Recent work in the area of transdermal peptide and protein drug delivery is overviewed, including strategies such as prodrugs, chemical enhancement, iontophoresis, electroporation, and ultrasound, with focus on mass‐transport mechanisms of different systems. Of the strategies studied, iontophoretic delivery appears the most promising. It is clear, however that more work remains to be done before transdermalpeptide and protein delivery devices come to market. Chemical engineers can contribute significantly to further research in this exciting area.