Biomedical Engineering Reference
In-Depth Information
proteins, and DNA can be modified, both at the cellular and organ levels, using
nano- or microparticle delivery systems [
17
-
19
]. For the development of effective
vaccines, biodegradable nanoparticles show great promise as vaccine delivery
systems. Controlled delivery systems consisting of nanoparticles can potentially
delivery either the antigens or adjuvants to the desired location at predetermined
rates and durations to generate an optimal immune response. The carrier may also
protect the vaccine from degradation until it is released. Other potential advantages
of the controlled delivery approach include reduced systemic side effects and the
possibility of co-encapsulating multiple antigenic epitopes or both antigen and
adjuvant in a single carrier. Biodegradable polymers provide sustained release of
the encapsulated antigen and degrade in the body to nontoxic, low molecular weight
products that are easily eliminated.
On the other hand, recent strategies for developing preventative and therapeu-
tic vaccines have focused on the ability to deliver antigen to dendritic cells (DCs)
in a targeted and prolonged manner. These strategies use nanoparticles because
they can achieve longevity on intact antigen to increase the opportunity for DC
uptake and processing. DCs are the most effective antigen-presenting cells
(APCs), and have a crucial role in initiating T-cell-mediated immunity. DCs
can control a substantial part of the adaptive immune response by internalizing
and processing antigens through major histocompatibility complex (MHC) class I
and class II pathways, and then presenting antigenic peptides to CD4
+
and CD8
+
T
lymphocytes (Fig.
1
)[
20
]. Therefore, targeting DCs with an antigen delivery
system provides tremendous potential in developing new vaccines [
21
]. Antigen
uptake by DCs is enhanced by the association of the antigens with polymeric
nanoparticles. The adjuvant effect of particulate materials appears to largely be a
consequence of their uptake into DCs. More importantly, particulate antigens
have been shown to be more efficient than soluble antigens for the induction of
immune responses [
22
,
23
]. Furthermore, the submicron size of nanoparticles
offers a number of distinct advantages over microparticles, and nanoparticles
generally have relatively higher intracellular uptake as compared to
microparticles [
24
,
25
]. There are several factors that can affect the immune
response induced by immunization with particulate antigens. Among them are
particle size, the chemical structure of particles, surface hydrophobicity, zeta
potential, and adjuvants used within the formulations.
This review focuses on biodegradable polymeric nanoparticles as vaccine delivery
systems and immunostimulants, and summarizes the preparation of antigen-conjugated
particles and the mechanism of nanoparticle-based vaccines. Using these systems, it
is possible to target antigen delivery to APCs, activate these APCs, and control
intracellular release and distribution of the antigen. By understanding immune
activation, we can rationally design particulate adjuvant to not only deliver antigen
but also to directly activate innate immune cells providing the pro-inflammatory
context for antigen recognition. The generation of more potent particulate adjuvants
may allow the development of prophylactic and therapeutic vaccines against
cancers and chronic infectious diseases.
