Transdermal delivery of peptide and protein drugs: Strategies, advantages and disadvantages

Peptide and protein drugs (PPDs) that possess the advantages of high specificity and tolerance, and low immunogenicity can effectively treat diabetes, osteoporosis, cancer, and genetic defects. However, the high molecular weight and poor stability of PPDs lead to low bioavailability in oral delivery of these drugs and poor compliance of patients with subcutaneous injection, which greatly limit their clinical applications. Transdermal drug delivery has the characters of low invasiveness, low cost and simple operation, and it is easy to implement self-management of patients, reduce the risk of infection, and improve compliance of patients. However, the transdermal delivery of hydrophilic and macromolecular PPDs is difficult to penetrate the barrier of the stratum corneum. Recently, various novel strategies have been developed for percutaneous delivery of PPDs to the systemic circulation, which are summarized in this review. The mechanism, advantages and limitations of these strategies are also discussed.