Biomedical Engineering Reference
In-Depth Information
particles that enter via the airways. Alveolar macrophages that trap pathogens then
enter into the lymphatic capillaries where they drain into the pulmonary network of
lymph nodes (both in the pleura and in the upper airways). Here they are presented
to T lymphocytes that facilitate an immune response against the pathogen. The
lungs therefore represent an alternate route for the delivery of vaccines that avoids
the use of needles since the induction of an immune response in one mucosal mem-
brane transfers immunity to other mucosal membranes. It is also this dense distribu-
tion of macrophages that makes the lungs a potential target for the uptake of
particulate nanomedicines from the blood. This can be achieved to a certain degree
by conjugating surface targeting ligands that make nanoparticles more attractive to
alveolar macrophages such as mannose. For instance, the uptake of rifabutin via the
lungs after IV administration can be improved by associating the drug with man-
nosylated lipid nanoparticles that display equivalent biodistribution to the liver and
lungs (Nimje et al.
2009
).
3
Particle Properties That Mediate Reticuloendothelial Uptake
3.1
Nanoparticles and Colloids That Target
the Reticuloendothelial System and the Role
of Opsonisation
Since the RES is designed to protect the body against invading pathogens and other
foreign materials, any properties of an administered nanomedicine that indicates
that the particle or macromolecule is foreign will make it susceptible for RES
uptake. Nanomedicines, depending on definition, range in size from 1 to 1,000 nm
in diameter. In comparison, the diameter of a virus particle can range from 25 nm
to approximately 120 nm and the diameter of a bacterium can range from 200 to
250 mm. Thus, particulate nanomedicines typically have a size that mimics that of
a pathogen. This alone does not determine the ultimate fate of a nanomedicine,
since particulate nanomedicines have been administered that demonstrate very
good biocompatibility and very limited uptake by organs of the RES. The surface
characteristics of the material also strongly influence the RES targeting capacity of
a nanomedicine, either by promoting opsonisation that essentially tags the particle
for removal by macrophages, or by acting as ligands to receptors expressed on the
macrophage surface. Receptor mediated processes will be discussed in a later section
of this chapter.
It is important, however, to have an understanding of the opsonisation process.
The surface of a macrophage is anionic as are the surfaces of many pathogens. This
dictates that binding of a pathogen with the macrophage membrane would be unfa-
vourable on purely electrostatic grounds. Thus, prior modification of the pathogen
surface is required to enable phagocytosis of these species which would otherwise
be repelled from the macrophage surface. Opsonisation is a process whereby a
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