Pharmaceutical Manufacturing Handbook: Production and

pseudostratifi ed epithelium comprising three types of cells: olfactory receptor cells,
supporting cells, and basal cells. The receptor cells are elongated bipolar neurons
located in the middle stratum of the epithelium, interspersed among the sustentacular
cells; the microvilli cover the supporting cells, which extend from the mucosal
surface to the basal membrane; while the basal cells are located in the basal surface
of the neuroepithelium. These basal cells go on to differentiate, becoming new
receptor cells [140, 185, 186] . The surface of the nasal cavity measures about 180 cm 2
in humans as compared to about 10 cm 2 in rats, and the olfactory region is reported
to constitute about 3% of the nasal cavity in humans and 50% in rats. Some other
differences include the fact that in adult humans the volume of CSF is about 160 mL
while it is only about 150 μ L in rats; also, the CSF is replaced about three times daily
in humans, whereas in rats it is replaced hourly. Hence, though there is suffi cient
evidence regarding nose - to - brain delivery, especially in rats and in some cases in
humans, the impact of these factors on the interpretation of the results between the
two species could be signifi cant [155, 187] .
5.6.9
NASAL DELIVERY OF VACCINES
NASAL DELIVERY OF VACCINES 633
The discovery of vaccines for smallpox, cholera, and typhoid and the variety of vaccines
now available have led to a signifi cant reduction in the mortality and morbidity
due to many diseases, with smallpox being the fi rst to have been completely eradicated
and poliomyelitis targeted to be the next. At present, the World Health Organization
is working toward the complete elimination of poliomyelitis throughout
the world [188, 189] . However, since Jenner discovered the vaccine for smallpox
more than two centuries ago [190] , only some 50 vaccines have been approved for
use, and few additional vaccines have been discovered. Most of those in current use
are administered parenterally; they can induce only a systemic immune response,
not mucosal immunity. Obviously the latter is very important in the prevention and
treatment of infectious diseases, be they due to viral, bacterial, or parasitic pathogens
that attack via the mucosal surfaces [190] .
The criteria to be met in designing a vaccine formulation include the following:
The vaccine should have the capacity to produce lifelong immunity, be able to act
against the different strains and variants or the subtypes of the organisms, be effective
in all age groups, be able to act quickly and also to induce immunity in the fetus
when the mother is treated, be able to act effectively after a single treatment, and
ideally be administered noninvasively. Finally, such a vaccine must be relatively
inexpensive and remain active under a variety of conditions, especially not requiring
the cold chain [191] .
The following section addresses the need for needle - free vaccines with formulations
based on safer adjuvant and delivery systems.
5.6.9.1 Nasal Vaccines: Ideal Noninvasive Route
When we talk about targeting the pathogens entering through the mucosal surfaces,
the route that usually comes to mind is the oral route. However, this route has its
drawbacks for several reasons, such as the fact that the antigen used is degraded
along with the gastric contents; furthermore, there is also the diffi culty of reaching
the antigen - presenting cells [192] . In comparison to the oral route, nasal vaccination