SYSTEMIC DELIVERY OF PEPTIDES AND PROTEINS ACROSS ABSORPTIVE MUCOSAE

As therapeutic peptides and proteins become readily available through rapid advances in recombinant technology, and because rapid presystemi c elimination renders them ineffective when administered orally, pharm aceutical scientists are faced with the challenge of delivering these macromolecules systemically; therefore, alternative routes of delivery need to be investigated. Transmucosal delivery through absorptive muc osae represents one of these alternatives. This route has the advantag e of being noninvasive and of bypassing hepatogastrointestinal clearan ce. The absorptive mucosae that have been investigated for delivery of peptides and proteins include buccal, nasal, pulmonary, rectal, and v aginal. Nasal delivery has been studied extensively and has been the m ost successful-nasal sprays for buserelin, desmopressin, oxytocin, and calcitonin are already available commercially. In general, enzyme inh ibitors and permeation enhancers need to be coadministered for success ful delivery of these biopharmaceuticals. Classes of enhancers used fo r transmucosal delivery include bile salts, dihydrofusidates, cyclodex trins, surfactants, and chelating agents. Each of these agents exerts its enhancing effects by a different mechanism, and each has been asso ciated with adverse effects. This article discusses the physiology of each of the mucosae used, the fundamentals of transmucosal delivery, a nd recent progress in systemic delivery of therapeutic peptides and pr oteins across each of the mucosae; in an effort to highlight principle s of transmucosal delivery, it also discusses the transmucosal deliver y of enkephalin, calcitonin, and insulin as case studies.