Biology Reference
In-Depth Information
FIGURE 15.1
Gerald Weissmann (1930
e
). Courtesy of John Simon Guggenheim Memorial Foundation.
For centuries many famous historical figures suffered from gout. Included in this list are
Henry VIII, Issac Newton, Thomas Jefferson, Benjamin Franklin, Charles Darwin, and
even 'Sue', the famous Tyrannosaurus Rex skeleton. So, what is responsible for gout? It is
known that gout is related to a rich diet, perhaps one that is based on red meat dripping
with cholesterol. Men 'take the gout', but young women do not. However, post-menopausal
women do get gout. Also, it is a historical fact that eunuchs (castrated males) do not 'take the
gout'. Weissmann therefore proposed that gout was related to cholesterol and testosterone,
but not estrogen. Gout is also associated with accumulation of uric acid crystals. Weissmann
proposed that uric acid crystals attach to the lysosomal membrane containing cholesterol
and testosterone, making the organelle very leaky to the sequestered hydrolytic enzymes.
Once released from the lysosome, the enzymes destroy the cell, inducing gout. To test this
hypothesis, Weissmann made 'boy' (containing testosterone) and 'girl' (containing estrogen)
cholesterol-enriched liposomes. Upon the addition of uric acid the 'boy' liposomes, but not
the 'girl' liposomes, became leaky to a sequestered solute. This clever experiment accounts
for the basic characteristics of gout. Years later, Weissmann developed two liposome-
encapsulated drugs (Abelcet and Myocet, see
Table 15.1
).
2. Liposomes
Soon after their discovery by Alec Bangham in 1961, it became evident that the basic
properties of liposomes (discussed in Chapter 13) make them ideally suited for a plethora
of medical applications
[2,3]
. Liposomes are tiny, sealed lipid vesicles that have a sequestered
aqueous space for water-soluble (hydrophilic) drugs and a surrounding, largely imperme-
able lipid bilayer membrane that can simultaneously house lipid-soluble (hydrophobic)
drugs and an external facing surface that can be modified with specific ligands (
Figure 15.2
,
[4]
). Valuable liposome properties include:
1.
They can be made from thousands of natural and artificial lipids.
2.
They exist in lipid bilayers and so resemble biological membranes.
3.
They are generally not antigenic.
4.
They can be made in a wide range of sizes.
5.
They can be made with a range of different sequestered volumes.
