Biomedical Engineering Reference
In-Depth Information
proven useful in reducing the uptake of a variety of nanoparticles by the RES
organs, the appropriate choice of lipid in the construction of the particle can simi-
larly minimize or indeed increase the extent of RES targeting. This is particularly
relevant for intravenous delivery systems that require extended plasma circulation
times and subcutaneous delivery systems that may be used to improve drug uptake
into the lymphatic system or specifically into regional lymph nodes. Much of the
literature surrounding the influence of lipid composition on the affinity of colloids
for the RES is based on liposomes. Hence, Fig. 11 depicts some of the lipids com-
monly used to generate liposomes.
As mentioned previously, the biodistribution of liposomes to the liver and spleen
can be increased via the incorporation of phosphatidylserine into the lipid bilayer
that increases the uptake of liposomes via fixed macrophages (Oussoren and Storm
1997 ). However, liposomes based entirely on DPPC also display avid uptake into
both lymph nodes and the spleen after subcutaneous administration, even though
most of the dose remains at the injection site after more than 2 days (Oussoren and
Storm 1997 ). This effect is abrogated via the concurrent use of DPPC and choles-
terol (Oussoren and Storm 1997 ). In general, however, increased plasma circulation
times and minimized RES uptake appear to be achieved when using lipid composi-
tions that include phosphatidylcholine, phosphatidylglycerol and sphingomyelin,
although in each situation, RES uptake is generally best minimized by the incorpo-
ration of a hydrophilic or alternate biocompatible polymer into the outer surface
(Oussoren and Storm 1997 ; Spanjer et al. 1986 ).
5
Summary
In the majority of applications of nanomedicines, extended blood circulation times
are required. Consequently RES uptake is a major drawback in the use of nanopar-
ticles as drug delivery systems, and increased uptake by the RES organs has the
potential to be associated with increased delivery of drug to organs that may be
sensitive to the toxic effects of the drug. As a general rule, the more 'foreign' the
particle looks the greater the potential for RES uptake. Examples include increased
particle surface charge (that may mediate particle opsonisation or increased adhe-
sion to the surface of macrophages and other tissues), increased size and the use of
structural materials that promote receptor mediated recognition of the particle by
one or more cells within the RES. The flip side to this rule is in instances where
improved nanoparticle targeting to particular cells within the RES, particularly
macrophages, are desired. Examples of these are in the improved delivery of anti-
gens to immune cells in order to enhance the immunization process or where deliv-
ery of antiretrovirals to macrophages may improve the resistance of the cells to
viral attack or replication. Examples of such modifications have been given.
However, where RES uptake is not desired, steps can be taken to minimize the
susceptibility of nanoparticle systems for uptake via these organs. These include
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