Biomedical Engineering Reference
In-Depth Information
of various lung-related disorders (viz. asthma, cystic fibrosis, bronchitis, cancer), pulmonary drug
delivery allows the administration of high concentrations of drugs directly to the intended site of
action. In this way, it provides a rapid onset of action with minimal side effects that are usually
elicited by the systemic administration of drugs [9]. Furthermore, it also improves the therapeutic
efficacy by by-passing the hepatic first-pass metabolism of the liver as well as the poor absorption of
the intestines that is associated with oral drug delivery, thus allowing for similar therapeutic effects
from a smaller dose.
For systemic administration, pulmonary drug delivery offers a noninvasive mode of delivery
with low enzymatic activities or hepatic first-pass metabolism of drugs (Byron and Patton, 1996). It
should also be considered that the macromolecules delivered by other routes are seldom absorbed
into systemic circulation, while the delivery by the lungs allows for more effective absorption
[10,11]. Since the pulmonary route avoids the introduction of bioactives to the gastrointestinal tract,
reproducible absorption kinetics usually are achieved due to the lack of interference from the varia-
tions in an individual's diet and metabolic system [12,13].
Among the various drug delivery systems considered for pulmonary applications, nanocarriers
demonstrate several advantages for the treatment of respiratory diseases. For example, nanocarriers
may provide prolonged drug release and cell-specific, targeted, drug delivery. The development of
an innovative nanocarrier, able to deliver the drug to the desired site of action, is highly dependent
on the nature of the active substance and on its desired site and mode of action (Figure 11.1). The
pulmonary system is in direct contact with the environment and represents a promising gate of entry
into the body for therapeutic compounds.
11.2 ANATOMY AND PHYSIOLOGY OF THE PULMONARY SYSTEM
By removing metabolic wastes (CO
2
) and maintaining the pH of the body, the pulmonary system
is one of the most crucial organ systems of the body. The respiratory zone is chiefly divided into
the upper and lower airways with the larynx and trachea as the line of junction [14,15]. Together
with the nose, mouth, pharynx, and larynx, the upper airways frame the air transportation sys-
tem, while the lower respiratory tract consists of trachea-bronchial, gas-conducting airways, and
gas-exchanging acini. The lower airway is further divided into the conducting, transitional, and
respiratory zones. The conducting zone is responsible for the bulk movement of air and blood. The
conducting airways exhibit 16 bifurcations, followed by another 6 bifurcations of the respiratory
bronchioles, facilitating the passage of air to the respiratory zone where the alveolar ducts—with
alveolar sacs—finally branch off.
The respiratory zone is mainly composed of respiratory bronchioles and alveoli where gas
exchange takes place [16]. The bronchial tree begins with the trachea, which bifurcates to form the
main, left, and right primary bronchi (Figure 11.2). Each primary bronchus divides into still smaller
secondary bronchi, or lobar bronchi—one for each lobe of the lung. The secondary bronchi branch
into many tertiary bronchi that further branch several times, ultimately giving rise to tiny bronchi-
oles that subdivide many times, finally forming terminal bronchioles and respiratory bronchioles.
Each respiratory bronchiole subdivides into several alveolar ducts that end in clusters of small, thin-
walled air sacs called alveoli, which open into a chamber called the alveolar sac [17,18].
Alveoli are the terminal air spaces of the respiratory system and are the actual sites of gas exchange
between the air and the blood. Approximately 100 million alveoli are found in each lung. Each alveo-
lus is a thin-walled, polyhedral chamber of approximately 0.2 mm in diameter (Figure 11.2). Each
alveolus is confluent with a respiratory bronchiole at some point by means of an alveolar duct and an
alveolar sac (Figure 11.3). Airway epithelium is composed of a variety of cell types, the distribution
of which confers different functions according to the airway region [18,19]. The human lung consists
of 5 lobules and 10 bronchopulmonary segments, and, adjacent to each segment, lung lobules are
present that are composed of 3-5 terminal bronchioles. Each bronchiole is composed of the smallest
structural unit of the lung, the acinus, which consists of alveolar ducts, alveolar sacs, and alveoli.
