Poly(Alkyl Cyanoacrylate) Nanosystems - Intracellular Delivery: Fundamentals and Applications - page 239

sizes of nanoparticles obtained with these polysaccharides were 137 and 170 nm
using 10,000 Da dextran and 20,000 Da chitosan (Bertholon et al. 2006b ). The size
of nanoparticles synthesized with chitosan 20,000 g/mol can be reduced to 62 nm
by addition of 3% pluronic F68 in the emulsion polymerization medium (De
Martimprey et al. 2010 ). Using hyaluronic acid (HA), average diameters of the
nanoparticles can be modulated from 290 to 325 nm by playing with the HA/ n BCA
molar ratio (He et al. 2009 ).
Finally, regarding the drug loading, chitosan coated nanoparticles can easily be
loaded with siRNA by adsorption on preformed nanoparticles. These nanoparticles
were able to deliver active siRNA to a subcutaneously implanted tumor after intra-
venous administration (De Martimprey et al. 2010 ). Paclitaxel was encapsulated
with a maximal encapsulation efficiency of about 90%. In vitro release studies
demonstrated that HA modification efficiently reduced the initial burst release in
the first 10 h and provided a sustained release in the subsequent 188 h (He et al. 2009 ).
Doxorubicin, another first line anticancer agent, could not be loaded in PIBCA
nanoparticles by encapsulation because the drug is susceptible to oxidation by the
cerium ions used to initiate the free radical polymerization. However, it could be
associated by adsorption with the same loading performance and releasing features
than those of the corresponding nanoparticles obtained by zwitterionic/anionic
emulsion polymerization (Alhareth et al. 2011 ).

4.2.3 Self-Assembly of Preformed (co)Polymers

An alternative to the preparation of PEGylated PACA nanoparticles by direct polym-
erization in aqueous dispersed media is the use of preformed amphiphilic copolymers
able to self-assemble in water (Choi et al. 1995 ; Peracchia et al. 1997a, 1998, 1999 ;
Deng et al. 2005 ). Stable nanospheres in the 100-700 nm range were obtained from
PIBCA- b -PEG diblock copolymers, either by nanoprecipitation or by emulsification/
solvent evaporation (Choi et al. 1995 ). As explained in the Chapter from Vauthier
and Bouchemal of this topic, these methods can be adapted to produce large quanti-
ties of nanoparticles making possible their industrial development. It was shown that
the copolymer compositions played an important role on the colloidal characteristics
of the nanospheres. P(HDCA- co -MePEGCA) copolymers also demonstrated suit-
able amphiphilicity to form stable nanospheres of 100-200 nm in diameter upon
nanoprecipitation which exhibited a biodegradable PHDCA core and a shell of
excretable PEG chains (Peracchia et al. 1997a, 1998, 1999 ). Interestingly, it was
shown that P(HDCA- co -MePEGCA) nanoparticles exhibited a significant ability to
cross the blood-brain barrier (BBB), compared to non-PEGylated counterparts and
nanoparticles with preadsorbed surfactants such as polysorbate 80 or poloxamine
908 (Brigger et al. 2002 ; Calvo et al. 2001, 2002 ; Garcia-Garcia et al. 2005a, b ). This
was explained by a specific adsorption of apolipoprotein E and B-100 (Apo E and
B-100) onto these PEGylated nanospheres, leading to their translocation mediated
by low-density lipoprotein receptors (LDLR) (Kim et al. 2007a, b, c ). Following this
discovery, the encapsulation into these nanoparticles of didanosine (ddI) prodrugs,