Biomedical Engineering Reference
In-Depth Information
Pluronic-stabilized polypropylene sulfide nanoparticles of 20, 45, and 100 nm
diameter were prepared to compare the effective targeting of DCs in lymph nodes
[
173
,
174
]. Among the three different sizes of nanoparticles, 20 nm-sized
nanoparticles were the most readily taken up into the lymphatics via interstitial
flow, and activated lymph node-residing DCs more efficiently than the other sizes
of nanoparticles. Different sized antigen-conjugated carboxylated polystyrene
nanoparticles were also investigated for their size-dependent immunogenicity
in vivo. The optimal size for an effective immune response was narrowly defined
at 40-50 nm, in the viral range [
175
]. Furthermore, it has been reported that the size
of antigen-loaded PLA particles modulated the immune response [
25
]. Immuniza-
tion with PLA nanoparticles (200-600 nm) was associated with higher levels of
IFN-
g
production related to the T helper 1 (Th1)-type immune response. In contrast,
immunization with PLA microparticles (2-8
m
m) promoted IL-4 secretion related
to the Th2-type immune response. Gutierro et al. also demonstrated that the
vaccination of 1,000 nm-sized BSA-loaded PLGA particles generally elicited a
higher serum IgG response than that obtained with the vaccination of 500 or 200
nm-sized particles, the immune response for 500 nm particles being similar than
that obtained with 200 nm by the subcutaneous and the oral route, and higher by the
intranasal route [
171
]. The vaccination of 1,000 nm particles generally elicited a
higher serum IgG response than that obtained with the vaccination of 500 or
200 nm-sized particles, the immune response for 500 nm particles being similar
than that obtained with 200 nm by the subcutaneous and the oral route, and higher
by the intranasal route. These results suggest that the biodistribution of nano- and
microparticles and the particle-related immune response can be regulated by
controlling the size of the particles. Consequently, the size of the particulate
delivery system is an important factor for modulating immune responses via
differential interactions with APCs.
6 Concluding Remarks and Future Perspectives
Biodegradable nanoparticles with entrapped vaccine antigens, such as proteins,
peptides and DNA, have recently been shown to possess significant potential as
vaccine delivery systems. There are three primary mechanisms of adjuvant func-
tion: (1) stabilization of antigen, (2) delivery of antigen, and (3) activation of innate
immunity. The duration of delivery is likely to affect immunity. Delivery of antigen
is particularly important in cases where the vaccine is intended to act through DCs,
as is the case for new vaccine applications requiring cell-mediated immunity.
Nanoparticles are extremely flexible delivery systems capable of encapsulating a
wide range of antigens. Improving delivery to DCs by nanoparticles will improve
vaccine efficiency. Nanoparticle-based vaccine systems will also reduce the vac-
cine dosage frequency and will increase patient compliance. In the near future,
these vaccine systems can be used for treating many infectious diseases or cancers.
