ABSTRACT
Delivery of therapeutic peptides and proteins faces formidable barriers and, therefore, a parenteral dosage form is typically developed, as discussed in Chapter 6. However, because of issues relating to short half-lives and inconvenient administration, alternative routes are being actively investigated. Efforts to develop oral dosage forms have been discussed in Chapter 7. Some of the other mucosal routes that have not yet been discussed include nasal, pulmonary, rectal, buccal, and ocular routes. These mucosal routes will be discussed in this chapter. Of these routes, pulmonary and nasal appear to be most promising and will be discussed in greater detail. The primary barriers to mucosal delivery are the absorption and enzymatic barriers. A drug has to overcome the epithelial absorption barrier by passing through the cells (transcellular transport) or through the tight junctions between the cells (paracellular transport). The equivalent pore radius of the various mucous membranes is an important limiting factor and varies from 4 to 8 Å (Zhou, 1994). Another barrier to mucosal absorption of peptides and proteins is the proteolytic barrier (Eppstein & Longenecker, 1988; Lee, 1988; Reddy & Banga, 1993). Proteolytic enzymes are present all over the body, and they act by hydrolyzing the peptide bonds in polypeptides. Proteolysis may occur at N-terminus or C-terminus or at distinct endo-residues in a polypeptide. The presence of these enzymes is essential to sustain vital body processes, but these enzymes present a formidable barrier to the delivery of peptides and proteins.
