Biomedical Engineering Reference
In-Depth Information
release kinetics, stability, degeneration of carrier systems, hydration behavior,
electrophoretic mobility, porosity, specifi c surface characteristics, density, crystal-
linity, contact angle, and molecular weight [50]. Yet, the
in vivo
behavior of MNPs
also depends on the dose and administration route (oral or parenteral, including
delivery routes such as intravenous, pulmonary, transdermal, and ocular), in addi-
tion to less conventional routes, for example when used as scaffold coatings [51].
For biomedical applications, MNPs should be stable at room temperature in
water or at neutral pH, they should not aggregate, and they should be biocompat-
ible. Whilst the colloidal stability will depend on the particle size (i.e., it must be
suffi ciently small so as to avoid sedimentation due to gravity), it will also depend
on the charge and surface chemistry, which in turn give rise to steric and coulom-
bic repulsions [52, 53] .
Another important criterion for the surface-coating is that it should be physio-
logically well tolerated; for example, dextran-magnetite has been reported to have
a low toxicity index (LD
50
) [54], though this has been the subject of much debate.
In general, when the MNPs are injected into the bloodstream they are rapidly
coated by plasma proteins; this process, known as opsonization, is critical in dictat-
ing the fate of the injected particles [55]. Normally, opsonization will render the
MNPs recognizable by the reticuloendothelial system (RES), which serves as the
body's major defense system. The RES is a diffuse system of specialized cells that
are phagocytic (i.e., they engulf inert material) and are in association with the
connective tissue framework of the liver, spleen, and lymph nodes [56, 57]. The
macrophage (Kupffer) cells of the liver, and to a lesser extent the macrophages of
the spleen and circulation, therefore play a critical role in the removal of opsonized
particles. As a result, the application of nanoparticles, either
in vivo
or
in vitro
,
requires a surface modifi cation that will ensure the particles are biocompatible,
and are also less prone to opsonization and thus phagocytosed to a lesser degree
by the RES.
The MNPs' surface coatings play an essential role in retarding clearance by the
RES. Uncoated MNPs were shown to be absorbed by the mononuclear phagocyte
system after systemic administration, followed by clearance by the liver, spleen,
and bone marrow. Different proteins (antibodies) of the blood serum (opsonins)
bind to the surface of foreign bodies, accelerating phagocytosis of the particles. In
order to avoid detection by the RES, biodegradable (e.g., dextran) and nonbiode-
gradable organic and inorganic coatings can be used. However, PEGylated sur-
faces in particular have demonstrated the desired protein- resistant characteristic,
this having been attributed to the combination of a low interfacial energy in water
and a steric stabilization effect [58].
Whereas, MNPs with hydrophobic surfaces are effi ciently coated by plasma
components and thus rapidly removed from the circulation, those particles which
are more hydrophilic can resist this coating process and are cleared more slowly
[59]. This effect has been used to advantage when attempting to synthesize RES-
evading particles by sterically stabilizing the particles with a layer of hydrophilic
polymer chains [60]. For example, the most common coating materials are deriva-
tives of dextran, PEG, polyethylene oxide (PEO), poloxamers and polyoxamines
