Protein and Peptide Delivery through Respiratory Pathway - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 437

BBB. Delivery of genes and DNA plasmids, insulin-like growth factor-I, and inter-
feron-beta (IFN) into the CNS system by intranasal administration has been studied,
and a higher distribution to the brain indicates nasal administration as a promising
route for the delivery of therapeutic agents because it bypasses the BBB and has
reduced side effects in other organs [42-45] .
9.5.2 Structure and Function of the Human Nasal Cavity
The human nasal cavity has a total volume of about 16-19 ml, and a total surface
area of about 150-180 cm 2 (measured using a computed tomography scan). The nasal
septum divides the nasal cavity along the center into two halves, one opening to the
facial side and one to the rhinopharynx, through the anterior and via the posterior
nasal apertures, respectively. The nasal septum is not very accessible for the penetra-
tion of drugs into the human system because it consists mostly of cartilage and skin.
The volume of each cavity is approximately 7.5 ml, having a surface area around
75 cm 2 [46] . The most efficient area for drug administration is the lateral walls of the
nasal cavity, which consist of highly vascularized mucosa.
The vestibular region is present at the opening of nasal passages lined with kera-
tinized stratified squamous transitional epithelium with no or few cilia [47,48] .
These cells also contain vibrissae, or nasal hairs, for filtering out airborne particles.
Drug deposition in this region will remain stationary, be sucked along the floor to
the pharynx by sniffing, drip out, or wiped off. The vestibule includes an important
region called the nasal valve, which is the narrowest segment in the respiratory tract,
accounting for 80% of nasal resistance and 50% of total airway resistances. The nasal
valve is a dynamic valve involved in the regulation of nasal airflow and filtering of air-
borne particles. The challenges for delivering therapeutics to the target sides beyond
the nasal valve have recently been published. The vestibular region is considered to
be the least important of the three regions with regard to nasal drug absorption. The
olfactory region, situated in the upper part of the nasal cavity, is a specialized area
responsible for olfaction, has surface area 10 cm 2 , and plays a vital role in the trans-
portation of drugs to the CNS along the intraneural/extraneural olfactory pathway.
The olfactory epithelium is innervated by the lamina propria of the olfactory epithe-
lium located beneath the epithelial layer(s); it contains blood vessels, mucus-secreting
acinar glands (Bowman's glands), nasal lymphatics, and a neuronal supply consisting
of olfactory axon bundles, autonomic nerve fibers, and the maxillary branch of the
trigeminal nerve [46,49-51] . These nerves are responsible for the transport of drugs
from the nasal cavity to the CNS along the intraneural-extraneural olfactory path-
way. Olfactory epithelial deposition may also involve drug delivery via the trigeminal
nerve, although there is no evidence at present to support this mechanism. The tri-
geminal nerve is the largest of the cranial nerves and, among other functions, enables
sensory perception in the nasal cavity. The trigeminal nerves innervate the entire nasal
mucosa. They have three major branches, namely, the ophthalmic nerve, maxillary
nerve, and mandibular nerve. The ophthalmic and maxillary branches of the trigemi-
nal nerve are important for nose-to-brain drug delivery because neurons from these
branches pass directly through the nasal mucosa. Hence, in contrast to the rostral