Biomedical Engineering Reference
In-Depth Information
allergen therapy, and vaccine delivery to manipulate the immune system for
enhanced therapeutic benefits as well as minimize side effects. In addition, dif-
ferent NMs are suitable for tracking that also allows the tracking of any material
that is loaded in them to evaluate the correct migration of the NMs to its target.
Antigen interactions with different engineered NMs such as dendrimers,
polymer, metallic NMs, MNMs, and QDs are important considerations in
designing their particular medical applications. Thus, this chapter will focus on
several NMs that will be used for immunotherapy. Two particular areas that will
be discussed are nanoimmunotherapy for allergy and for cancer.
The oral route for allergen degradation is the most often used route because
of convenience, safety, and because it is the least expensive. However, the
disadvantages of oral immunotherapy for allergen degradation within the gut
results from the gastric acidity or to the presence of proteolytic enzymes.
100
Clinical trials applying oral immunotherapy techniques for allergens were very
poor.
101,102
Although some studies have shown a significant improvement of
the allergic symptoms,
103,104
they had to administer high doses of allergen to
observe successful treatment. At a lower dose of allergen, it would be essential
to use an appropriate adjuvant to increase the immune response and prevent the
allergen degradation in the gastrointestinal tract.
105
The only adjuvant that is currently approved for human use is alum which
had been demonstrated to have no capacity to elicit sufficient mucosal immune
response and it is ineffective when administered by oral route.
105,106
Some
mucosal adjuvants have been described such as monophosphoryl lipid A
(MPL), CpG oligonucleotides or particulate mucosal delivery adjuvants such as
immune-stimulating complexes (ISCOMs)
105,106
but these have limited efficacy
when administered orally.
107-109
The use of adjuvants for delivery system with
controlled release delivery systems in the form of micro
110
or NPs
111
as adjuvant
have been proposed because they can potentially: (i) protect the loaded antigen
from enzymatic degradation in the gastrointestinal tract, (ii) prolong immune
response, (iii) enhance the delivery to the cells and gut associated lymphoid tis-
sue (GALT), (iv) reduce the number of dosage.
111,112
Several groups have studied the use of various NPs for immunotherapeutic
applications.
61,67,73,84,95,105,111,113-116
The group of Salam used poly(methyl vinyl
ether-comaleic anhydride, MW 200,000 to demonstrate bioadhesive capacity
and high affinity toward normal mucosal tissue and Peyer's patches.
117
The
group of Gomez
105
studied the immunotherapeutic effect when administered
by oral route to a model of sensitized mice and demonstrated that poly(methyl
vinyl ether-comaleic anhydride (Gantrez
®
AN)) NPs protected the sensitized
mice from death by anaphylactic shock by using OVA complexed with NMs.
Chitosan, a cationic polysaccharide derived from the crustacean shell chitin
is biocompatible
118,119
and in the form of NPs (100-200 nm), it has been used to
deliver plasmids.
94,120
Chitosan has wound healing,
121
stimulation of the immune
system,
122
anticoagulant,
123
antimicrobial,
124
and is non-toxic in humans.
73
In
humans, it is non-hemolytic, weakly immunogenic, and slowly biodegradable
