Biomedical Engineering Reference
In-Depth Information
microparticles were placed in the in-house inhalation apparatus and the animals
inhaled the powder during 1930s. Microparticles targeted macrophages and not
epithelial cells on inhalation. Drug concentrations in macrophages were ~20 times
higher when microparticles were inhaled rather than free drug solutions.
Microparticles were thus suitable for enhanced targeted drug delivery to lung mac-
rophages (Muttil et al.
2007
).
In the following study, a comparison between PLGA and alginate microparticles
was established. RIF, INH and PYZ were loaded in mass median aerodynamic
diameter 1.1 mm alginate microparticles and administered by nebulization (Ahmad
et al.
2005
). Drug concentrations were detected in plasma after 3 h, which was
faster than PLGA microparticles. Also, INH, RIF and PYZ were detectable up to
14, 10 and 14 days, respectively, as opposed to the fast clearance of the free drugs
after 12-24 h. Nebulization of drugs-loaded alginate nanoparticles (one dose
biweekly, three doses) over the course of 45 days was as effective in clearing the
lungs and the spleen of
M. tuberculosis
-infected guinea pigs as 45 oral daily doses
of the free drugs. Therefore, alginate microparticles could also be suitable for inter-
mitent treatments.
Different cyclodextrins (CDs) were used to elaborate pharmaceutical formula-
tions of hydrophobic drugs for the inhalation route. The short-term toxicity of such
formulations administered by inhalation to C57BL/6 mice was tested (Evrard et al.
2004
). Hydroxypropyl-b-CD (HP-b-CD), g-CD, as well as randomly methylated
b-CD (RAMEB) aqueous solutions can undergo aerosolization; the resulting
droplet-size ranges were compatible with pulmonary deposition.
In vivo
, it was
demonstrated that short-term exposure to inhaled HP-b-CD, g-CD and RAMEB
solutions are non-toxic after assessing bronchoalveolar lavage, lung and kidney
histology, bronchial responsiveness to methacholine and blood urea. The only
change noted was a slight increase in lymphocyte count in the bronchoalveolar
lavage after HP-b-CD and g-CD inhalation. Therefore, CDs are useful in signifi-
cantly enhancing the solubility of apolar drugs with a view to inhalation therapy
although an increase in lymphocyte counts in the bronchoalveolar lavage after CDs
inhalations needs further investigations.
3
Salmonella spp
Salmonella
enterica are facultative intracellular, motile Gram negative anaerobes
bacteria that cause a variety of diseases in humans and animal hosts. Salmonella
serovar falls into two general categories: those that cause enteric (typhoid) fever in
humans (
S. typhi
and
S. parathyphi
) and those that do not (
S. enteritidis
and
S. typhimurium
). Enteric fever is a systemic illness characterized by a high sus-
tained fever, abdominal pain and weakness. Millions of cases of enteric fever are
reported annually throughout the world and without antimicrobial therapy the mor-
tality rate is 15% (Hook
1990
). Nontyphoidal serovars of
S. typhimurium
produce
an acute gastroenteritis, characterized by intestinal pain and non bloody diarrhea,
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