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to the amino group of the amino acid. Cationic formulations including
these bivalent galactolipids (cationic lipid 2D3, DOPE and 0 to 5% of
galactoside) were exposed to a ricin agglutination test, which revealed the
accessibility of the galactoside residues. These formulations were not
evaluated in transfection assays; however, a competitive inhibition in the
presence of free galactose as determined by the agglutination test, con-
firmed the specificity of the ligand/receptor binding at the liposome stage.
Triantennary galactosyl ligand conjugated to a PEGylated lipid
(Fig. 25) permitted enhancement of DNA expression in the case of Gal/
GalNAc receptor expressing cells (HepG2).
66
These in vitro experiments
demonstrated the importance of the PEG-type spacer providing a better
accessibility of the ligand at the surface of the lipoplexes for a subsequent
ligand/receptor interaction.
However, increasing the number of galactoside residues on the
multivalent scaffold did not always increase the transfection eciency of
hepatocytes cells (Fig. 26). Indeed, the use of a ligand equipped with five
OH
HO
N
O
O
HO
S
O
OH
O
O
OH
HO
O
O
NH
NH
O
O
HO
S
O
OH
O
O
O
OC
18:1
O
H
H
O
O
45
OC
18:1
OH
HO
O
O
NH
S
O
HO
OH
O
Fig. 25 Structure of a trivalent galactosyl derivative.
O
H
H
H
O
OH
HO
O
O
HO
S
OH
O
HO
OH
HO
OH
O
O
S
O
O
HO
HO
S
O
O
HO
OH
O
HO
OH
HO
S
O
OH
S
HO
O
OH
HO
HO
Fig. 26 Structure of a pentavalent galactosyl derivative.
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