Biomedical Engineering Reference
In-Depth Information
demonstrated that the
g
-PGA-Phe nanoparticles are also effective for vaccines
against human immunodeficiency virus (HIV) [
150
,
151
], influenza virus
[
152
,
153
], Japanese encephalitis virus [
154
], human T-cell leukemia virus type-I
(HTLV-I) [
155
], or cancers [
146
,
156
,
157
]. The antigen-loaded
g
-PGA-Phe
nanoparticles can provide a safe antigen delivery and adjuvant system for vaccina-
tion against viral infections or tumors because of their biocompatibility and biode-
gradability [
158
-
161
].
5.2 Vaccination Using Antigen-Loaded PLGA Nanoparticles
PLGA or PLA nano- and microparticles are suitable vehicles for the delivery of
recombinant proteins, peptides, and pDNA to generate immune responses in vivo.
Several studies have shown that PLGA nanoparticles can be used to modulate
immune responses against encapsulated antigens due to their ability to efficiently
target APCs and to facilitate appropriate processing and presenting of antigens to T
cells [
93
,
162
-
170
]. Gutierro et al. investigated the immune response to BSA-
loaded PLGA nanoparticles after subcutaneous, oral, and intranasal administration
to evaluate parameters that can affect the immune response [
171
]. These parameters
include size, the internal structure of nanoparticles, surface hydrophobicity, zeta
potential, and co-encapsulated surfactants, adjuvants or excipients during formula-
tion, which are known to influence targeting strategies.
Many different vaccine antigens encapsulated into PLGA nanoparticles were
shown to induce broad and potent immune responses. For example, hepatitis B
therapeutic vaccines were designed and formulated by loading the hepatitis B
core antigen (HBcAg) into PLGA nanoparticles (300 nm) with or without
monophospholipid A (MPLA) adjuvant [
172
]. A single immunization with HBcAg-
encapsulating PLGA nanoparticles containing MPLA induced a stronger cellular
immune response than those induced by HBcAg alone or by HBcAg mixed with
MPLA in a murine model. More importantly, the level of HBcAg-specific immune
responses could be significantly increased further by a booster immunization with the
PLGA nanoparticles. These results suggested that co-delivery of HBcAg and MPLA
in PLGA nanoparticles promoted HBcAg-specific cellular immune responses. These
findings suggest that appropriate design of the vaccine formulation and careful
planning of the immunization schedule are important for the successful development
of effective therapeutic vaccines for hepatitis B virus.
5.3 Effect of Particle Size on Nanoparticle-Based Vaccines
To design optimal drug carriers, polymeric nanoparticles have the advantage of
being able to regulate their physicochemical properties, such as particle size, shape,
surface charge, polymer composition, hydrophobicity, and biodegradability.
In particular, a method for regulating the size of polymeric nanoparticles is
essential for effective vaccine delivery, and to elicit a specific immune response.
