Transdermal drug administration routes limitations

One of the key pieces to development of a successful drug product is the ability to deliver the drug to the site of action with minimal discomfort or inconvenience to the patient. For small molecule therapeutics, there is a wide range of options available for drug administration. Delivery via injection (IV, IM, and SC), oral, nasal, ocular, transmucosal (buccal, vaginal, and rectal), and transdermal routes is possible with small molecule drugs. However, the size of proteins and the complexity of their structures severely limit the routes of administration available to proteins. 

The relatively non-invasive nature of transdermal drug delivery, and the fact that this route can simultaneously avoid problems associated with presystemic metabolism and mimic (at least, to some extent) parenteral input profiles, are significant advantages. There have been, therefore, diverse attempts to exploit the skin for peptide and protein delivery. As we have noted before, transdermal administration, with or without one or more enhancement technologies, will always be limited to potent drugs and this accounts, once more, for the effort devoted to peptide and protein (i.e., typically very active substances) administration via this route. 

The low oral bioavailability of hormone-replacement drugs due to intestinal and first-pass metabolism requires the use of higher doses of these drugs, which are associated with many side effects. Parenteral administration of sex steroids as well as use of the transdermal route has been viewed as an alternative. However, the transdermal route has certain limitations, such as the visibility and palpability of the patch as well as possible skin irritation. These drawbacks have limited the use of this route. The intranasal route has therefore been considered as an alternative [128],... 

---