Protein and Peptide Delivery through Respiratory Pathway - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 438

Figure 9.1 Anatomy of the nose:
1. atrium, 2. nasal vestibule, 3. respiratory
region (3-a. superior turbinate, 3-b. middle
turbinate, 3-c. inferior turbinate),
4. olfactory region, 5. nasopharynx.
entry of a drug via the olfactory pathway, the trigeminal nerve was shown to enhance
nose-to-brain delivery to caudal brain areas [52] . Portions of trigeminal nerve enter
the brain both through the pons and separately through the cribriform plate under
the olfactory bulbs, and deliver the drug to the upper spinal cord and the brain [53] .
The three distinct anatomical regions present in the nasal cavity and a cross-sectional
sketch of it are shown in Fig. 9.1 .
The surface of the epithelia in the nasal cavity is covered by a continuous layer
of mucus, which entraps the particles. It is secreted by the various mucosal and sub-
mucosal glands and is composed of two layers: hypophase and epiphase. A watery
hypophase, is adjacent to the epithelial surface floating on a more viscous gel like
epiphase. Numerous enzymes such as cytochrome P450, enzyme isoforms (CYP1A,
CYP2A, and CYP2E), carboxylesterases, and glutathione transferases are found in
the nasal cavity [54-56] .
9.5.3 Barriers to Nasal Drug Delivery
Successful nasal drug therapy, specifically of proteins and peptides, depends on sev-
eral barriers or factors that affect drug permeability through the nasal mucosa. These
are broadly classified into three categories ( Fig. 9.2 ): biological-, formulation-, and
delivery device-related factors.
9.5.3.1 Biological Factors
Several approaches have been made to date to mutate the nasal structural features so
as to increase drug permeability across nasal mucosa. However, these are not advis-
able during chronic applications as they can result in inadvertent adverse effects due
to alterations in the normal physiology of the nasal cavity.
9.5.3.1.1 Structural Characteristics
The structural features of the regions are responsible for the permeability of the nasal
cavity. The type of cells, density and number of cells present in the specific nasal