ABSTRACT
Over the last several years, therapeutic peptides and proteins have gained increasing importance as a result of rapid strides in the biotechnology industry. Therapeutic application and market introduction of this new generation of therapeutic agents requires parallel development of ef•cient delivery systems by the pharmaceutical industry. Because of their polypeptide nature, peptide and protein drugs are destroyed in the gastrointestinal (GI) tract and must be administered parenterally. These are invasive routes that involve the inconvenience of injections and add to the cost of the health-care system if administered under medical supervision. Thus, noninvasive methods of administration would be preferred (1). Skin, with its accessibility, enormous surface area, and possibility for site targeting, offers a potential means for noninvasive delivery. Several drugs are now available on the market as transdermal patches. However, none of these is a peptide or protein drug. This is because skin is ordinarily permeable only to small lipophilic molecules, a criterion readily ful•lled by drugs, such as nitroglycerin, scopolamine, clonidine, and nicotine. Peptide and protein drugs, being hydrophilic and macromolecular in nature, do not readily permeate the skin. The transdermal route offers some distinct advantages for the delivery of peptide drugs, in addition to the general advantages of transdermal delivery discussed in Chapter 1. Because these drugs have short half-lives, the greatest bene•t would be the fact that the transdermal route provides a continuous mode of administration, somewhat similar to that provided by an intravenous infusion. Transdermal delivery of peptides may become feasible if assisted by enhancement means such as iontophoresis, microporation, electroporation, jet injectors, phonophoresis, or chemical enhancers (2,3). Each of these techniques has advantages and disadvantages. Iontophoresis is generally believed to work best for polypeptides with a molecular weight less than ~10 kDa, but recent literature has reported delivery of proteins up to 14 kDa (4,5). On the other hand, microchannels created by microporation technologies are several microns in dimensions and, therefore, will enhance delivery, as there are no limitations with respect to molecular size.
