Biomedical Engineering Reference
In-Depth Information
ultradeformable liposomes also showed non-photodynamic leishmanicidal activity.
Confocal laser scanning microscopy of cryosectioned human skin mounted in non-
occlusive Saarbrücken Penetration Model, showed that upon transcutaneous admin-
istration Zn phthalocyanine penetrated nearly ten folds deeper when incorporated
in ultradeformable liposomes that if loaded in conventional liposomes. Quantitative
determination confirmed that when loaded in ultradeformable liposomes phthalo-
cyanine penetrated homogeneously in the
stratum corneum,
carrying seven folds
higher amount eight folds deeper than conventional liposomes. It is envisioned that
the multiple leishmanicidal effects of ultradeformable liposomes contaning phtha-
locyanine could play a synergistic role in prophylaxis or therapeutic at the first
stages of the infection.
8
Trypanosoma Cruzi
The causative agent of Chagas disease is the flagellate protozoan
Trypanosoma
cruzi
which is transmitted to the human by hematophagous reduviidae bugs.
T. cruzi
infect 10-12 million people in endemic areas of Latin America with 15,000
deaths each day (Clayton
2010
). Transmission is associated with the faeces of tri-
atomine bugs (>80%), blood transfusion or organ transplant (~15%) (Leiby et al.
2002
), congenital transmission (the parasite crosses placenta) (4%), ingestion of
contaminated food (<1%) and laboratory accidents (<1%) (Strosberg et al.
2007
).
After entering a mammal through a skin wound or a mucosal membrane, trypomas-
tigote forms of
T. cruzi
invade many different cell types. In the cytoplasm, it is
transformed in
amastigotes
that multiply by means of binary fission producing cell
lysis, and releasing new
trypomastigotes
into the blood stream that can invade any
nucleated cell to begin a new reproductive cycle. After the generally asymptomatic
acute phase (characterized by detectable parasitemia of
trypomastigotes
) that lasts
from a few weeks to several months, the infection is well controlled by the host
immune response. Nevertheless, without specific treatment during the acute phase,
the infection progresses to a long chronic asymptomatic period, this may last for
years. It is estimated that in one-third of those infected develops clinical symptoms
of different degrees of severity, which include cardiomyopathy, heart failure and
digestive-tract abnormalies such megacolon and megaoesophagous, will appear in
what is known as symptomatic chronic Chagas disease (Andrade et al.
1996
; Sosa
Estani et al.
1998
). This irreversible structural damage to the heart, the oesophagus
and the colon, with severe disorders of nerve conduction in these organs are caused
by the intracellular
amastigotes.
In contrast to Leishmania,
T. cruzi
parasites are not only taken up by phagocytic
cells via classic phagocytosis, but can also actively invade cells by induced phago-
cytosis (Nogueira and Cohn
1976
).
T. cruzi
induce the recruitment of lysosomes by
a unique calcium-regulated microtubule-mediated pathway. The binding of
T. cruzi
to cells causes a transient increase of intracellular calcium, which induces actin
disruption and the movilization of lysosomes along microtubules towards the site
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