Biology Reference
In-Depth Information
FIGURE 15.2
Drug de-
livery using liposomes. Lipo-
somes are tiny, sealed lipid
vesicles that have a seques-
tered aqueous space for
water-soluble (hydrophilic)
drugs and a surrounding,
largely impermeable lipid
bilayer membrane that can
simultaneously house lipid-
soluble (hydrophobic) drugs
and an external facing surface
that can be modified with
specific ligands. Reproduced
with permission
[4]
.
list of liposome-sequestered drugs is shown in
Table 15.1
. A few applications of liposome-
sequestered drugs follow.
3. Leishmaniasis
Whereas the RES presents a substantial hurdle for most intravenous applications of target-
ing with drug-encapsulated liposomes, it is actually advantageous for certain diseases. The
best known of these is leishmaniasis, a serious, mostly tropical disease
[6]
. While rare in the
United States, leishmaniasis has been reported in immigrant populations, returning tourists,
and military personnel from the Persian Gulf. Leishmaniasis (also known as kala-azar, black
fever, and Dumdum fever) is the second greatest parasitic killer in the world (after malaria)
and affects about 12 million people worldwide, with 1.5
2 million new cases reported each
year. Sadly, leishmaniasis is often fatal. Historically, the most effective anti-leishmaniasis
drugs are antimonial compounds that unfortunately have about the same inherent toxicity
as arsenates. The cure can be as bad as the disease!
In the late 1970s Carl Alving (
Figure 15.3
) proposed an unusual solution that was based on
the life cycle of the leishmaniasis protozoan parasite
[7]
. The disease is spread by the bite of
a female sandfly, whereupon the protozoan is rapidly taken up by the victim's macrophage
(part of the RES) where they multiply. Alving noticed that when liposomes were injected intra-
venously, they were rapidly taken up by the same RES macrophages. He reasoned that seques-
tering the antimonial drugs into liposomeswould target the drugs directly to the parasite living
e
