Biomedical Engineering Reference
In-Depth Information
conformations; either stretched chains or loops depending on the number of terminal
hydroxyl groups present in the PEG (Peracchia et al.
1997b
).
Whereas early work reported the use of b-cyclodextrine as a surface-modifier/
surfactant for the anionic emulsion polymerization of
n
BCA (Douglas et al.
1985
),
different kinds of polysaccharide were also used to replace traditional PEG coat-
ings. It yielded stable 100-500 nm PACA nanospheres were obtained with surface
properties governed by the nature of the polysaccharide (Yang et al.
2000
; Bertholon
et al.
2006b, 2005
; Labarre et al.
2005
; Bravo-Osuna et al.
2007b
; Shirotake et al.
2008
; Duan et al.
2009, 2010
; Kulkarni et al.
2010
). Interestingly, when covered by
chitosan, the resulting cationic nanoparticles served as a colloidal scaffold for the
preparation of nanoparticle/DNA complexes by the complex coacervation of nano-
particles with the DNA (Duan et al.
2009
).
Anionic miniemulsion polymerization was recently employed to prepare
PEGylated P
n
BCA nanocapsules with an oily core and loaded by paclitaxel (Zhang
et al.
2008
). The oily core was formed by a medium-chain triglyceride and the
anionic polymerization of
n
BCA was initiated at the oil/water interface by MePEG
via its alcoholate chain-end. MePEG-
b
-P
n
BCA block copolymers surrounding the
oily core were thus formed
in situ
.
4.2.2
Free-Radical Polymerization
Free-radical emulsion polymerization of alkyl cyanoacrylates initiated by the
polysaccharide/cerium IV (Ce
4+
) ions redox couple was also undertaken leading to
stable nanospheres (Chauvierre et al.
2003b
). Whereas zwitterionic/anionic emul-
sion polymerizations gave polysaccharides compact loops at the nanoparticle sur-
face due to the
in situ
synthesis of grafted copolymers, the free-radical process led
to polysaccharides-based block copolymers and thus to hairy nanospheres due to a
different initiation mechanism (Fig.
9
) (Chauvierre et al.
2003a, 2004, 2007
;
Bertholon et al.
2006a, b
; Bravo-Osuna et al.
2007a, c
). One interest of making
PACA nanoparticles by free radical polymerization is to obtain nanoparticles with a
different conformational arrangement of the polysaccharide chains at the nanoparticle
surface compared to that obtained with zwitterionic/anionic emulsion polymerization.
Indeed, this was found critical to control interactions of the nanoparticles with serum
proteins giving different complement activation pattern hence influencing the pharma-
cokinetics and the biodistribution of an associated drug. For instance, nanoparticles
obtained by free radical polymerization behaved like stealth nanoparticles (Bertholon
et al.
2006b
; Alhareth
2010
; De Martimprey et al.
2010
; Vauthier et al.
2011
).
It is noteworthy that free radical polymerization of alkyl cyanoacrylates can only
be promoted at pH 1 by taking advantage of an extremely fast free-radical polymer-
ization initiation (Chauvierre et al.
2003b, c
). The low pH is mandatory to delay the
zwitterionic/anionic polymerization initiation to let a narrow time window of 5 to
10 min to initiate the free radical polymerization. In the emulsion polymerization
conditions this requirement is fulfilled at pH 1. The polysaccharide/cerium IV (Ce
4+
)
ions redox couple was found appropriate to initiate the free radical polymerization in
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