Biomedical Engineering Reference
In-Depth Information
infections such as sinusitis, bronchitis, and 6-12% of community-acquired
pneumonias (Grayston et al. 1989, 1993 ), as well as chronic, persistent and often
asymptomatic infections (Hammerschlag et al. 1992 ) Persistent C . pneumoniae
infection has been associated with chronic human diseases, including atherosclero-
sis, arthritis and asthma (Cook et al. 1998 ; Danesh et al. 2000 ).
All Chlamydiae undergo an unusual biphasic developmental cycle, which is of
great relevance when considering the design of novel drug delivery strategies
(Whittum-Hudson and Hudson 2005 ). After the attachment of the infectious form
of the organism to the outer membrane of susceptible host cells, the organism sub-
sequently produces cytoplasmic inclusions known as elementary body. These ele-
mentary bodies reside within a vacuole termed an inclusion and subsequently
develop into the non-infectious, metabolically active form called the reticulate
body. Reinfection occurs after reticular bodies dedifferentiate back to elementary
bodies and are released back into the tissue milieu by host cell lysis. The three spe-
cies can cause systemic disease by hematogenous spread. Respiratory secretions
transmit C. pneumoniae from human to human.
5.1
Conventional Treatments
Treatment is empirical. Doxycycline is the drug of choice except in children
younger than 9 years and in pregnant women. If symptoms persist, a second course
with a different class of antibiotics is usually effective. Telithromycin is the first
antibiotic in a new class called ketolides and is approved for C. pneumoniae pneu-
monia by the US Food and Drug Administration. Fluoroquinolones, including
levofloxacin and moxifloxacin, also have some activity, although less than that of
tetracyclines or macrolides (Yuji 2010 ).
5.2
Preclinical Delivery Systems
Core-shell polymeric microparticles consisting of water soluble, hydrofluoroal-
kane-philic biodegradable copolymer of chitosan, and PLA shell and a core of
PLGA nanoparticles were employed for pulmonary delivery by MDI. The PLGA
nanoparticles were entrapped within these micron-sized particles whose shell is
designed to be well-solvated by the propellant, and thus to provide adequate physi-
cal stability to the formulation, and consequently good aerosol characteristics.
Dispersions of the core-shell particles in hydrofluoroalkane propellant revealed
enhanced physical stability compared to PLGA nanoparticles alone, and more
importantly, excellent aerosol characteristics as determined by inertial impaction
studies. The shell is soluble in water and breaks down releasing the core. These
microparticles were specially designed to target region in the upper airways instead
of the alveolar region. In the upper airways, microparticles break down, the core is
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