ABSTRACT
Acknowledgment................................................................................................................ 388
References .......................................................................................................................... 388
By virtue of their size and charge, peptidemolecules are not the ideal candidates for transfer into
the systemic circulation following instillation in the nose. Among the many barriers to absorp-
tion that must be overcome are mucociliary clearance, extracellular enzymatic destruction, the
lipophilic bilayer membrane of nasal epithelial cells, the potential for nasal epithelial cells to
degrade any peptide molecules that cross the lipid bilayer, and the potential to establish futile
cycles of endocytosis and exocytosis on the apical surface of polarized epithelial cells. Indeed,
in the face of these multiple barriers, it seems all the more remarkable that any substantial
absorption of peptide drugs from the nose has ever been observed.Despite these barriers, recent
reports have confirmed that many peptide drugs, ranging in sizes up to 30,000 Da, have been
successfully delivered through the nasal route when they were formulated with an absorption-
enhancing agent [1-3]. This chapter will focus on the unique barriers to be overcome and the
therapeutic opportunities that are now becoming available as a result of successful nasal
delivery of peptide drugs. Currently, the vast majority of nonpeptide therapeutic drugs admi-
nistered nasally are administered to patients for local effects, rather than systemic effects.
However, some small nonpeptide drugs, such as cocaine, are delivered nasally to produce
effects elsewhere in the body. Characteristically, the absorption of peptide and nonpeptide
drugs administered by the nasal route displays a very rapid pharmacokinetic profile and avoids
first-pass metabolism of the drug by the liver [1,4-6]. Numerous different types of absorption-
enhancing agents that improve the bioavailability of peptide drugs have now been described
[1-14]. This chapter will discuss these agents in some detail, in so far as they have been shown to
increase peptide drug absorption from the nasal cavity. Several review articles have been
published on the topic of peptide drug delivery through the nasal route [2,9,12,15-17]. This
chapter will build on this information and focus on recent developments in the field of peptide
drug delivery. Current nasal peptide products and novel peptide drugs that are likely candidates
for future development into nasal therapeutic agents will be discussed.
