Protein and Peptide Delivery through Respiratory Pathway - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 439

Figure 9.2 Barriers to nasal drug delivery.
regions, nasal volume and length, nasal epithelial surface area, bend(s) in the airway
from nostril to nasopharynx, structure of turbinates, presence of a complete/incom-
plete septum, cellular structure, subepithelial structure, including blood supply, mem-
brane transport, etc. influence the drug absorption following intranasal administration.
9.5.3.1.2 The Biochemical or Enzymatic Barrier
Although the method of administering drugs nasally avoids the problem of extensive
metabolism in the GI tract and first-pass metabolism in the liver, the drugs may be
susceptible to the enzymes of nasal mucosa. These include oxidative and conjugative
enzymes (e.g., glucuronyl transferase and glutathione transferase), cytochrome P450,
carboxylesterases, aldehyde dehydrogenase, carbonic anhydrase, exopeptidases and
endopeptidases (e.g., aminopeptidase, carboxypeptidase, trypsin-like activities, and
cathepsins) as well as others [57,58] . These enzymes degrade the drugs within the
nasal mucosa, causing a pseudo-first-pass effect. Nasal proteases and peptidases
have been implicated in poor absorption of peptidic drugs, such as calcitonin, insulin,
LH-RH, and desmopressin [59-62] . Various approaches such as the use of protease