Biomedical Engineering Reference
In-Depth Information
Tomayo et al. have also reported that poly(anhydride) nanoparticles act as
agonists of various TLRs. The nanoparticles were useful as Th1 adjuvants in
immunoprophylaxis and immunotherapy through TLR exploitation [
120
].
Similar results have been obtained with PLGA nano- and microparticles [
121
,
122
], liposomes [
107
], cationic polystyrene microparticles [
123
], polystyrene
nanoparticles [
124
], and acid-degradable cationic nanoparticles [
125
]. Elamanchili
et al. examined DC maturation by PLGA nanoparticles. The results showed
that after PLGA nanoparticle pulsing, DCs exhibited a modest increase in the
expression of MHC class II and CD86 compared to untreated controls. In addition,
DCs pulsed with PLGA nanoparticles containing an immunomodulator,
monophosphoryl lipid A (MPLA), induced further DC maturation [
106
].
The PLGA-based nanoparticulate system offers the flexibility for incorporation of
broad range of TLR ligands. Copland et al. investigated whether formulation of
antigen in mannosylated liposomes enhanced uptake and DC maturation. Exposure
to liposomes containing OVA resulted in enhanced expression of maturation
markers when compared to exposure to antigen in solution. Expression was highest
following exposure to mannosylated liposomes [
107
]. These particulate systems
hold promise as a vaccine delivery system and immunostimulant. However, it has
also been reported that PLGA particles failed to mature DCs in vitro [
126
,
127
].
These differences may be attributed to particle size, particle concentration in DCs,
presence or absence of antigen, and experimental conditions.
3.4 Gene Delivery by Polyion Complex Nanoparticles
Gene delivery has great potential for the treatment of many different diseases. The
basic idea of gene therapy involves delivery of an exogenous gene into the cells to
express the encoded protein, which may be insufficiently or aberrantly expressed
naturally [
128
]. DNA delivery is, however, a difficult process and a suitable vector
is required for efficient protection as well as release. Both viral and nonviral vectors
have been used for gene delivery. Nonviral gene delivery relies on DNA condensa-
tion induced by cationic agents. Cationic polymers have been widely chosen to
condense DNA through electrostatic interactions between negatively charged DNA
and the positively charged cationic sites [
129
]. PIC nanoparticles composed of
g
-PGA and chitosan (CT) have been used as a DNA delivery system. CT/DNA
complex nanoparticles have been considered as a vector for gene delivery.
Although advantageous for DNA packing and protection from enzymatic degrada-
tion, CT-based complexes may lead to difficulties in DNA release at the site of
action. To improve the transfection efficiency of CT/DNA complexes,
g
-PGA/CT/
DNA conjugated nanoparticles were prepared by an ionic-gelation method for
transdermal DNA delivery using a low-pressure gene gun [
130
]. pDNA was
mixed with aqueous
g
-PGA (20 kDa). Nanoparticles were obtained upon addition
of the mixed solution to aqueous CT (80 kDa). The prepared
g
-PGA/CT/DNA
nanoparticles were pH-sensitive and had a more compact internal structure with a
