Biomedical Engineering Reference
In-Depth Information
18.2 SYNTHETIC IDENTITY OF POLYSACCHARIDE-COATED
POLY(ALKYLCYANOACRYLATE) NANOPARTICLES
Polysaccharide-coated poly(alkylcyanoacrylate) (PACA) nanoparticles have been utilized as drug
carriers for various purposes since 1979. Their design has evolved with time to adjust their proper-
ties with those required to fulfill different drug delivery strategies. These include functions required
to associate various types of drugs and the functionalities needed to adjust their
in vivo
biodistribu-
tion after IV administration. It leads to various types of PACA nanoparticles that are all spherical in
shape, but different in size, composition, and surface characteristics (Table 18.1).
In general, the size of polysaccharide-coated PACA nanoparticles ranges from a few tens of
nanometers (45-50 nm in diameter for the smaller) to several hundreds of nanometers (350-400 nm
in diameter for the larger). PACA nanoparticles are composed of copolymers, including at least
one segment of PACA and one segment of a hydrophilic macromolecule (Douglas et al., 1984;
Chauvierre et al., 2003; Bertholon et al., 2006a; Zandanel and Vauthier 2012). As depicted in Table
18.1, the copolymers take different structures depending on the conditions used for their synthesis.
Thanks to the amphiphilic properties of the copolymers, nanoparticles produced in an aqueous
medium occur as stable dispersions and take a core-corona structure. The hydrophobic segments
of the copolymers precipitate to compose the core of the nanoparticles while the hydrophilic part is
exposed at the nanoparticle surface (Figure 18.1).
This core-corona structure forms due to the thermodynamics of the system in the course of
nanoparticle synthesis, which evolves to obtain the more stable aqueous dispersion of nanoparticles.
A primary indication of the nature of the component included in the nanoparticle corona can be
given by measuring the zeta potential of the nanoparticles. In general, the zeta potential shown by
the nanoparticles is consistent with the value expected when considering the nature of the macro-
molecule (i.e., the polysaccharide) composing the hydrophilic part of the copolymer. Figure 18.2
gives examples of zeta potentials of PACA nanoparticles composed of copolymers including various
types of polysaccharides.
Some of the nanoparticles included in Figure 18.2 were prepared with blends of polysaccharides
and blends of polysaccharide and pluronic
®
F68. It is noteworthy that such nanoparticles display
intermediate properties when compared with those of nanoparticles obtained with each hydrophilic
macromolecule taken separately, indicating that they formed by the assembly of different copoly-
mers produced during polymerization.
The determination of the “synthetic identity” of nanoparticles in aiming to understand their
interactions with proteins requires a deeper description of their characteristics, especially of
the structure of their corona. Such efforts were carried out on PEG-coated nanoparticles and
nanoparticles coated with brushes of polyelectrolytes (Gref et al., 2000; Welsch et al., 2013).
Models of the chains' organization of PEG or polyelectrolytes could be suggested, providing
with a clear understanding of the nanoparticle surfaces' structures. In our work, we have char-
acterized a series of polysaccharide-coated PACA nanoparticles to provide with a comprehen-
sive view of the structure of the nanoparticle corona (Bertholon et al., 2006b; Vauthier et al.,
2009, 2011; Zandanel and Vauthier, 2012). In contrast with the polymers composing PEGylated
nanoparticles, polymers composing polysaccharide-coated PACA nanoparticles are synthesized
at the time of the nanoparticles' preparation by emulsion polymerization. This implies that the
structure of the copolymers composing the nanoparticles needs to be characterized from the
obtained nanoparticles. As in the case of many amphiphilic copolymers, the polysaccharide-
PACA copolymers composing the nanoparticles were difficult to characterize. The main dif-
ficulty arose from the fact that they were not soluble in solvents commonly used for polymer
analysis. The only solvent in which the nanoparticle-copolymers could apparently dissolve was
DMSO (dimethyl sulfoxide). However, obtaining a true solution in which polymer molecules
occur as single and well-individualized chains could only be obtained at a low concentration.
Above a concentration of 1.1 mg/mL, the copolymer molecules aggregated together, forming
