Biomedical Engineering Reference
In-Depth Information
the presently practiced subcutaneous route [143]. Also, levonorgestral liposomal DPI
has been found to be effective in female rats for contraception [144].
Leukotriene
inhibitors and antagonists in various phases of development have been
proposed to be effective antiasthmatic compounds [145]. Inhalation delivery of leu-
kotriene inhibitor Abbott-79175 resulted in drug concentrations 66% lower than the
peak levels obtained following intravenous administration [146]. Delivery of gene for-
mulations via aerosols is a relatively new field that is less than a decade old. However,
significant developments in aerosol delivery systems and vectors in this short span
of time have resulted in major advances toward possible applications in various pul-
monary diseases. Aerosol delivery of cationic liposomes complexed with chloram-
phenicol acetyl transferase gene encoding plasmid DNA to mice results in significant
expression of the protein in lungs, particularly in the bronchial epithelium. The trans-
gene expression was restricted to the pulmonary tissue, and there was no evident tox-
icity to the animals [147].
Clinical studies of insulin, DNase, heparin, IFN-
α
, leuprolide acetate,
α
1-anti-
trypsin, antibiotics, and IFN-
on a number of patients indicate that inhaling proteins
are safe whether the patient is healthy or diseased [148 - 154] . However, research
shows that if a patient has lost over 60% of lung functioning, no significant improve-
ment in the diseased state is possible either by pulmonary delivery or by injections.
Studies have also demonstrated that aerosolized macromolecules do not create any
safety issues or problems associated with throat irritation or cough. However, pro-
teins and peptides of large particle sizes (more than 5 mm) can cause cough regard-
less of composition, so it is essential that particle sizes be kept in the fine particle
range (less than 5 mm). Pulmonary delivery will doubtless become one of the leading
drug delivery alternatives with advances in pulmonary delivery technology.
γ
9.5.7 Airway Deposition of Inhaled Particles
The lung contains three basic components: air, blood, and tissue, for gas exchange
and efficient resistance to the movement of air and blood. The highly specialized
transport mechanism of mucociliary clearance removes particulate matter from
inhaled air. After entering the tracheobronchial (upper airways) of the lung, air passes
through a variety of regions before gas exchange in the blood. Similarly, inhaled
aerosol also leads to deposition primarily in the nose and the tracheobronchial area
[155]. However, mouth breathing deposits aerosol primarily in the lungs. Breathing
parameters (such as tidal volume and breathing frequency), respiratory tract morphol-
ogy (such as obstructive or inflamed airways), and aerosol characteristics (such as
particle size and airflow velocity) determine the distribution and deposition patterns
for aerosolized particles. The high momentum of the particles with increased inspi-
ration rate affects their distribution and deposition onto the upper airways and the
tracheobronchial tract [156]. Breath holding and deep breathing increase residence
time of aerosol particles in the airways, with sedimentation due to gravity deposit-
ing particles into the inner regions of the lungs. A limitation on these effects is the
need to avoid excessive hyperventilation. Less deposition of inhaled particles into the
peripheral and distal lungs was observed in constricted or inflamed airways [157].
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