Chemistry Reference
In-Depth Information
OH
OH
O
OH
O
O
4
Fig. 13 Structure of the synthetic fucosylated glycolipid used in DPPC-Fuc-E
4
-Chol
glycoliposomes.
during the liposome formation by an extrusion method which led to
different levels of eciencies. If the encapsulation rate of ampicillin
seemed to be not strongly affected by the change of phospholipidic
composition (4.8-13.9%), the encapsulation of metronidazole drastically
decreased in epikuron 170 liposomes (
o
1.5%) compared to those of
DPPC (11.2-13.0%). Furthermore, as observed with X-ray diffraction
measurements, the presence of metronidazole resulted in the disorgan-
isation of the phospholipid bilayers. Concerning the liposome-bacteria
interactions, the results obtained with epifluorescence microscopy from
labeled NBD-PC liposomes showed that the incorporation of fucosyled
neoglycolipids in the vesicle membrane facilitated interactions with the
bacteria either in their spiral or in their coccoid forms with strains ex-
pressing the babA2 adhesin gene. In addition, in vitro experiments with
liposomes containing ampicillin showed a clear antibacterial effect that
confirmed the interest of such an approach to fight against H. pylori.
The same authors also investigated intra-liposomal pH measurements
and agglutination assays to study more deeply the behavior of the gly-
cosylated liposomes in acidic conditions.
37
The glycosylated vesicles were
found to be quite stable and the pH of the internal aqueous compartment
remained close to 4 even when more acidic conditions were imposed to
the external phase (pH 1.2-2). Such a pH gradient depended essentially
on the nature of phospholipids used and was not extensively affected by
the incorporation of the targeting agent.
Shiga toxins (Stxs) are microorganisms involved in the pathogenesis of
hemolytic uremic syndrome (HUS) and severe systemic complications
following enterohemorrhagic Escherichia coli (EHEC) infection in
humans.
38
The toxins bind to specific glycolipids on the host cell, spe-
cifically galabiosyl (Gb2)-ceramide and globotriaosyl (Gb3)-ceramide
through interactions with eukaryotic cell-surface glycolipid receptors. It
is noteworthy that the clustering of Gb3 molecules is an important par-
ameter for inducing strong binding to Stxs. In light of these findings,
synthetic compounds mimicking the natural receptors have been in-
vestigated for eliminating Stxs from the intestine and/or neutralizing Stxs
in the circulation, as a therapeutic strategy for protecting patients from
serious Stx-mediated diseases. In particular, monovalent Stx-ligands of
phosphatidylethanolamine-dipalmitoyl-Gb3 (Gb3-PEDP) and galabiosyl
(Gb2)-PEDP (Fig. 14) were synthesized and formulated to provide glyco-
liposomes.
39
The concentrations of these glycoliposomes required to
neutralize the activity of Stx on a chosen cell line, HeLa229, were found to
be in the nanomolar range, meaning a neutralizing eciency that was
3-4 orders of magnitude higher, as compared with those of acrylic acid
copolymers incorporated with the Gb2, Gb3 ligands and the sugar
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