Biomedical Engineering Reference
In-Depth Information
released and penetrates mucus; its uptake by underlying epithelium is enhanced.
The core-shell particles thus formed provide for an opportunity to efficiently
deliver nanoparticles to the lungs, by enhancing their dispersibility in the propel-
lant, and by providing the appropriate aerodynamic size so as to enhance the aero-
sol characteristics of the corresponding MDI (fine particle fraction of 72% with a
mass median aerodynamic diameter of 2.3 mm).
In vitro
results reveal that nano-
particles from such core-shell formulations can be readily internalized by Calu-3
(airway epithelial) cells infected with
C. pneumoniae
, and more importantly, they
can gain access to chlamydial inclusions (Bharatwaj et al.
2010
; Lai et al.
2007
).
6
Plasmodium spp
Malaria is responsible for >300 million cases and more than one million deaths
each year (Gardella et al.
2008
) and is caused by four species of
Plasmodium
(
P. falciparum, P. vivax, P. malariae and P. ovale)
that enter the humans by the bites
of female mosquito of
Anopheles
genus.
P. falciparum
infection (80% of malaria
cases) cause severe malaria; neurological symptoms occur and may result in death
if treatment is not promptly instituted, especially in acute primary infections
(Whitty and Sanderson
1999
). The pathogenesis of cerebral malaria is multifacto-
rial, being caused by parasite sequestration and blockage of blood flow in small
vessels of the brain that includes clogging, sequestration, rosette formation, release
of cytokines, cerebral oedema, increased intracranial hypertension, etc. (Coltel
et al.
2004
; Pouvelle et al.
2007
).
P. vivax
and
P. ovale
infection cause chronic
malaria. The disease can relapse months or years after exposure, due to the pres-
ence of dormant liver stage parasites, named hypnozoites
.
Reactivation has been
reported for up to 30 years after the initial infection in humans.
P. malariae
pro-
duces long-lasting infections and if untreated can persist asymptomatically in the
human host for years, even a lifetime (Krettli et al.
2001
).
The inoculated sporozoites migrate to the liver and invade the hepatocytes by
mechanisms still not entirely understood (Krettli and Miller
2001
). A sporozoite
generates about 30,000 new invasive forms of the parasites (merozoites) in
9-10 days in the case of
P. falciparum
and 10,000 in 6-8 days in
P. vivax.
Released
merozoites enter erythrocytes and remain relatively inactive metabolically for
10-15 h (the ring stage). The parasite then undergoes a rapid phase of growth over
the next 25 h, forming the trophozoite stage, during which the parasite digests the
majority of the haemoglobin and grows to fill >50% of the volume of the host cell.
At the end of the trophozoite stage the parasite divides several times (the schizont
stage) before the host cell lyses (some 48 h after invasion) to release the newly
formed merozoites that continue the cycle. Some merozoites turn into male and
female gametocytes that also invade erythrocytes. This concerted cell lysis triggers
the classical malaria symptoms that are mainly headache, periodically recurrent
high fever (every 48-72 h), myalgia, anemia, hepato- and splenomegaly (Greenwood
et al.
2008
; WHO
2006
).
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