Biomedical Engineering Reference
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found in the various species that infect mammalian hosts. Recently, a peptide con-
taining the conserved region I amino acids (KLKQP) plus the basic amino acid
domain upstream from region I has been shown to bind strongly to affinity columns
of heparin and heparan sulfate (Ancsin and Kisilevsky
2004
). It is proposed that this
19-amino-acid sequence of the CSP of
P. falciparum
is at least partially responsible
for Plasmodium targeting
in vivo
by binding to the highly sulfated heparan sulfate
proteoglycans (HSPGs) found in liver (Ancsin and Kisilevsky
2004
; Lyon et al.
1994
). These HSPGs are located primarily on the basolateral side of the hepatocytes
and within the space of Disse (Frevert et al.
1993
; Pradel et al.
2002
). These 19 aa
peptide were attached to the distal end of a lipid PEG conjugate, and incorporated
to 100 nm LUV (Longmuir et al.
2006
). Due to the tendency of this targeting pep-
tide to induce rapid aggregation when the liposomes were mixed with serum, a rela-
tively high mole fractions of PEG5000 without peptide (10% mol PEG5000 plus
4% mol PEG3400-peptide) had to be added as well as employing long-chain C22:1
fatty acid as a lipid ingredient (82% mol). Fluorescently labelled liposomes
(Bodipy-TR-X) or liposomes containing gold-particle-labeled phosphatidyletha-
nolamine were i.v. administered to healthy mice. Fluorescence and electron micros-
copy demonstrated that the liposomes were accumulated both by non-parenchymal
cells (endothelial and Kupffer cells) and hepatocytes, with the majority of the lipo-
somal material associated with hepatocytes. Further works showed that liver cells
uptake was more than 600-fold higher than uptake by those in the heart, and more
than 200-fold higher than uptake by lung or kidney cells. Effective targeting to liver
in vivo
was successful after repeated (up to three) administrations to the host at
14-day intervals (Haynes et al.
2008
). Intracellular localization of drugs as well as
its antimalarial activity remained to be determined.
7
Leishmania spp
Leishmaniasis is caused by flagellated promastigotes of the
Leishmania
genus that
is injected in the skin by sandflies.
Leishmania spp
infect 12-14 million people
worldwide (Cunningham
2002
). Depending on the leishmania genus, different
clinical manifestations are produced: ulcerative skin lesions (cutaneous leishmania-
sis, caused by
L. amazonensis , L. mexicana, L. guyanensis, L. panamensis,
L. peruviana, L. venezuelensis and L. pifanoi
in America,
L. major, L. tropica and
L. aethiopica
in Europe), destructive mucosal inflammation (muco-cutaneous caused
by
L. braziliensis
in America), and disseminated visceral infection (kala-azar
caused by
L. donovani
in India and Bangladesh,
L. infantum
in rest of Asia, Africa
and Europe and
L. chagasi
in America) (Desjeux
2004
; Herwaldt
1999
).
Visceral leishmaniasis is mortal if untreated; cutaneous leishmaniasis heals by
reepithelisation with scarring, but it is treated to avoid disfiguring lesions; mucosal
leishmaniasis can produce potentially life-threatening inflammatory disease and
must be treated (Garcia and Bruckner
1997
; Murray et al.
2005
).
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