Biology Reference
In-Depth Information
immediately adjacent to the liposome surface
[9]
. This space ('periliposomal layer') makes it
difficult for a macrophage to bind to a liposome.
5. Stealth Liposomes
The importance of the GMI 'periliposomal layer' led to the idea of replacing the ganglioside
with a non-toxic synthetic polymer such as polyethylene glycol (PEG,
Figure 15.4
). PEG-lipo-
somes are usually referred to as 'Stealth Liposomes'
[12]
due to their ability to avoid the RES
and are heavily employed in many types of drug delivery. PEG is a linear polyether diol:
An important feature of PEG is the ability to be readily synthesized from short to very long
polymers and polymer length affects circulation longevity. PEG is normally anchored to the
liposome by attachment to the primary amine head group of PE (
Figure 15.5
):
In one example, Allen et al.
[13]
made liposomes from SM/PC/CHOL/DSPE-PEG where
the PEG length varied from short to long. They reported increased circulation longevity for
liposomes made from long length PEGs (PEG-1900 and PEG-5000) compared to short PEGs
(PEG-750 and PEG-120). While PEG increases circulation longevity, by itself it cannot speci-
fically target a particular cell. In fact, PEG actually hinders binding of the liposome to the
delivery site. Most PEG-liposomes are further modified by attachment of biological species
including monoclonal antibodies or fragments (immunoliposome), vitamins, lectins, specific
antigens, peptides, growth factors, glycoproteins, carbohydrates or other appropriate ligands
[14]
. The ideal situation would be to create a drug-carrying liposome that would be invisible
to the RES but would specifically bind to the diseased tissue or cell. The 'biological species' is
attached to the free end of the PEG in DSPE-PEG by a maleimide group. Transferrin is often
the ligand of choice for specific delivery of anticancer drugs. Modified liposomes are also
commonly used in diagnostic imaging and in vaccines (virosomes). Other synthetic poly-
mers, including poly(vinyl pyrrolidone) (PVP) and poly(acryl amide) (PAA), have been
tested as replacements for PEG, with some limited success.
6. Thermo-Liposomes
It is now well accepted that by using systemic chemotherapy for solid tumors, it is almost
impossible to achieve therapeutic drug levels without damaging healthy organs and tissues
FIGURE 15.4
Polyethylene glycol
[57]
.
O
O
H
P
N
O
OCH
3
O
O
O
O
O
-
O
O
n
O
FIGURE15.5
DSPE-PEG. Reprinted with permission
[58]
.
