Chemistry Reference
In-Depth Information
both hydrophobic and hydrophilic molecules. To deliver the molecules to the sites
of action, the lipid bilayer can fuse with other bilayers such as the cell membrane,
thus delivering the liposome contents. By making liposomes in a solution of DNA or
drugs (which would normally be unable to diffuse through the membrane), they can
be delivered (indiscriminately) past the lipid bilayer.
Liposomes can also be designed to deliver drugs in different specific ways.
Liposomes that contain low (or high) pH can be constructed in such a way that dis-
solved aqueous drugs will be charged in solution (i.e., the pH is outside the drug's
pI range) (isoelectric pH = pI). As the pH naturally neutralizes within the liposome
(protons can pass through a membrane), the drug will also be neutralized, allowing
it to freely pass through a membrane. These liposomes work to deliver drug by dif-
fusion rather than by direct cell fusion. Another strategy for liposome drug delivery
is to target endocytosis events. The size range of liposomes can be tailored so that
they are suitable for viable targets for natural macrophage phagocytosis. They are
then consumed while in the macrophage's phagosome. In this process, the drug is
target oriented.
Further, another important property of liposomes is their natural property to tar-
get cancer cells. The endothelial wall of all healthy human blood vessels are encap-
sulated by endothelial cells that are bound together by tight junctions. These tight
junctions block large vesicles of in the blood from leaking out of the blood vessel.
It is known that tumor vessels do not contain the same level of seal between cells,
and they are diagnostically leaky. The size of liposomes can be varied to suit a spe-
cific application. For example, liposomes of certain sizes (typically less than 400
nm) can rapidly enter tumor sites from the blood but are kept in the bloodstream by
the endothelial wall in healthy tissue vasculature. Liposome-based anticancer drugs
(Doxorubicin [Doxil] and Daunorubicin [Daunoxome]) are now being used as drug
delivery systems.
Liposomes can be created by shaking or sonicating phospholipids in water. Low
shear rates create
multilamellar
liposomes, which have many layers like an onion.
Continued high-shear sonication tends to form smaller
unilamellar
liposomes. In this
technique, the liposome contents are the same as the contents of the aqueous phase.
Sonication is generally considered a “gross” method of preparation, and newer meth-
ods such as extrusion are employed to produce materials for human use.
Further advances in liposome research have been able to allow liposomes to avoid
detection by the body's immune system. These liposomes are known as
stealth lipo-
somes
, and have been made with polyethylene glycol (PEG) studding the outside
of the membrane. The idea behind this is as follows. The PEG coating has been
found to exhibit neutral properties in the body. In other words, because of elec-
troneutrality, stealth liposomes do not attach to cells, and can circulate in the system
for much longer periods. The latter trait will ensure a longer circulatory life for the
drug delivery mechanism. Specific targeting is also used besides the PEG coating in
stealth liposomes. Such target-oriented liposomes are employed in delivering drugs
to the tissues where they are needed, since some drugs are indeed toxic at high con-
centrations. This is achieved by attaching a specific biological species to the lipo-
some, which enables it to bind to the targeted drug delivery site. Different targeting
ligands have been used (monoclonal antibodies, vitamins, or specific antigens) for
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