Biomedical Engineering Reference
In-Depth Information
opsonization. Here, the efficiency of the process is dependent on the poly-
mer type, their surface stability, reactivity, and physics (surface density and
conformation) [35]. Suppression of opsonization favors enhanced passive
retention of NPs at sites and compartments.
Prolonged circulation properties are ideal for slow or controlled release
of therapeutic agents into the blood to treat vascular disorders. Long cir-
culating particles may have application in vascular imaging, or even act as
artificial nanoscale red blood cells. Recent advances in synthetic polymer
chemistry afford precise control over the architecture and polydispersity of
polymers, polymer-conjugates, and block copolymers. Some of these novel
materials can form sterically stabilized nanoscale self-assembling structures
with macrophage-evading properties. Molecular signatures related to par-
ticular vascular and lymphatic beds and types of endothelial cells have been
identified, providing landmarks for circulating cells and molecules [37]. This
requires assembly of the appropriate targeting ligands on nanocarriers and
long circulating nanosystems. However, the ultimate characteristics such
as ligand density, spacing and conformation are dependent on ligand and
particle properties (curvature and surface reactivity). These modifications
determine the extent of particle stability and aggregation in vivo, as well as
the efficiency of receptor binding and follow up events, such as the mode of
particle internalization and associated signaling processes.
The macrophages represent a valid pharmaceutical target and there are
numerous opportunities for a focused macrophage-targeted approach [38].
Many pathogenic organisms have developed means of resisting macrophage
destruction following phagocytosis. Passive targeting of nanoparticulate ve-
hicles with encapsulated antimicrobial agents to infected macrophages can
represent a natural strategy for effective microbial killing [39]. Degradation
of the carrier by lysosomal enzymes releases the drug into the phagosome-
lysosome vesicle itself, or into the cytoplasm, either by diffusion or by specific
transporters depending on the physicochemical nature of the drug molecule.
Intravenous injection of tuftsin-bearing liposomes to infected animals have
not only resulted in delivery of liposome-encapsulated drugs to the mac-
rophage phagolysosomes, but also in the nonspecific stimulation of liver and
spleen macrophage functions against parasitic, fungal and bacterial infec-
tions [40]. Recently nanocarrier-mediated macrophage suicide (delivery of
macrophage toxins) has proved to be a powerful approach in removing un-
wanted macrophages in gene therapy and other clinically relevant situations.
Numerous polymeric and ceramic nanospheres, nanoemulsions, liposomes,
protein cage architectures, and viral-derived nanoparticles act as powerful
adjuvants, if they are physically or covalently associated with protein antigens
[41]. After endocytic uptake of nanoparticles, macrophages partially degrade
the entrapped antigens and channel peptides into the MHC molecules (class
I or II), for processing and presentation. Thus, there is considerable poten-
tial for nanoparticulate adjuvants for the development of new-generation
