Biomedical Engineering Reference
In-Depth Information
expanders following blood loss [38]. It should be noted, however,
that most, if not all, individuals produce antibodies of all isotypes
to dextran [39]. Formulations of dextran-coated particles used for
parenteral administration of iron suggest a more mixed outcome
with regard to tolerance compared with soluble dextran. Intolerance
to iron dextran complexes has been reported with an incidence of
approximately 0.6% of life-threatening anaphylactic reactions [40].
One explanation for the stronger reaction to the particle formulation
may relate to the generation of neo-epitopes on the particle surfaces
[41]. As discussed in more detail below, another aspect may pertain
to the molecular geometry of the interaction of antibodies with
dextran epitopes on the surface of a particle. While the anaphylactic
reaction presents a safety issue in the treatment with such particles,
surprisingly, the antibody-mediated opsonization may also serve an
important role in the function of these particles. Evidence suggests
that the application of USPIO particles as a contrast agent in magnetic
resonance imaging depends on the phagocytic uptake of these
particles. If so, the deposition of antibodies on the particles acts
to facilitate their function, which — both in imaging of the tumors
and in the case of neural imaging — to a large extent appears to rely
on the labeling of macrophages in zones of inflammation [42, 43].
This is situation is, of course, not necessarily to be encountered in
all settings where bioimaging or other applications of nanoparticles
are desired, and care must therefore be taken in evaluating the
pharmaceutical potentials of such particles.
A second frequently used biopolymer for making nanoparticles is
chitosan. Chitosan is made by de-acetylating chitin, mainly consisting
of N- acetyl-D-glucosamine, and derived from crustaceans, in particular
shrimp. Chitosan is composed of repeating units of D-glucosamine,
together with residual N- acetyl-D-glucosamine units. Because of the
charge of proteonated amine groups, chitosan polymers carry a high
positive charge, which is used for making relatively stable complexes
with nucleic acid polymers such as plasmidic expression vectors
and small interfering RNAs. From several animal studies, it is well
documented that chitosan particles are an excellent vehicle for the
transport of nucleic acid into several cell types [44]. Chitosan easily
triggers complement activation, probably in consequence of pre-
formed antibodies as well as the ability of MBL and ficolins to bind
N- acetyl glucosamine carbohydrate residues in the polymer [45]. As
in the case of dextran the ability of the immune system to respond to
 
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