Cell‐penetrating Peptides as a Novel Transdermal Drug Delivery System

In the last decade, almost one-third of the newly discovered drugs approved by the US FDA were biomolecules and biologics. Effective delivery of therapeutic biomolecules to their target is a challenging issue. Innovations in drug delivery systems have improved the efficiency of many of new biopharmaceuticals. Designing of novel transdermal delivery systems has been one of the most important pharmaceutical innovations, which offers a number of advantages. The cell-penetrating peptides have been increasingly used to mediate delivery of bimolecular cargoes such as small molecules, small interfering RNA nucleotides, drug-loaded nanoparticles, proteins, and peptides, both in vitro and in vivo, without using any receptors and without causing any significant membrane damage. Among several different drug delivery routes, application of cell-penetrating peptides in the topical and transdermal delivery systems has recently garnered tremendous attention in both cosmeceutical and pharmaceutical research and industries. In this review, we discuss history of cell-penetrating peptides, cell-penetrating peptide/cargo complex formation, and their mechanisms of cell and skin transduction.