Biomedical Engineering Reference
In-Depth Information
tissues or organs. For example, site-specific delivery to the lung provides a means to
target drug to the respiratory tract, thus avoiding unnecessary exposure to the rest of
the body. In general, the diseases associated with the respiratory system are treated
locally by inhalation of the medicament, which is predominantly dictated by mode of
inhalation, lung structure, and pathophysiology of the disease, in addition to the fac-
tors determining the aerodynamic behavior of the inhaled particles. For this reason,
an understanding of the physiological factors affecting lung structure is important for
successful drug targeting. The aerosol systems of bronchodilators are well established
for the treatment of asthma. Recently, the lung has been recognized as an efficient
route for systemic drug delivery, particularly of labile and refractory compounds such
as peptides and proteins.
9.3.1.1 Respiratory Tract Structure and Function
The main components of the respiratory system involved in gas exchange are air,
blood, and tissue. The mucociliary clearance mechanism removes particulate matter
from the inhaled air. Turbulence in the inspired air, disease condition, age, particle
size, and mucociliary clearance are the prime factors in determining drug retention
in the respiratory system. The presence of endogenous substances in the lung micro-
environment and the arterial blood supply to the airway mucosa play a critical role in
absorption, metabolism, redistribution, and activation or inactivation of inhaled drugs.
9.3.1.2 Ventilation and Perfusion
Many changes occur in lung volume with aging. Airways increase two to threefold in
diameter and lengthen symmetrically throughout the lung between birth and adulthood.
Airway resistance is much higher in infants due to the small absolute size of airways,
leading to more susceptibility to airway obstruction and wheezing. There is about a 50%
increase in residual volume by age 60, with a corresponding volume-related decline in
vital capacity, as the total lung capacity does not change. The resting lung volume, or
functional residual capacity, also increases with age, due to a loss of elastic recoil of the
lung. Further, the distribution of inspired air also tends to be more uniform in the supine
position than in the upright position. Airway mechanics and lung morphometry are
affected significantly by breathing pattern and disease. The key factors affecting repro-
ducibility of drug deposition site after inhalation are inhaled volume, flow rate, and
sustained breath holding at the end of inspiration. With increased inhaled volume, the
peripheral lung distribution of the particles increases, whereas with increased inhaled
flow rate, particles get deposited more in the oropharynx or in the large central airways
of the lungs by inertial impaction. A period of breath holding enhances deposition in
the more peripheral parts of the lungs by gravitational sedimentation.
9.3.1.3 Measurement of Airflow Obstruction
Resistance to airflow occurs throughout the respiratory tract, approximately half of the
total airway resistance occurs in the upper airways (larynx and above) and the remain-
ing in the lower airways.
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