Poly(Alkyl Cyanoacrylate) Nanosystems - Intracellular Delivery: Fundamentals and Applications - page 234

Fig. 7 Nanospheres (NS), water-containing nanocapsules (w-NC) and oil-containing nanocap-
sules (o-NC)
2010 ). Average diameters obtained by this process usually range from 50 to
300 nm, which is a well-adapted window for drug delivery purposes (Douglas et al.
1985 ; Alonso et al. 1990 ; Seijo et al. 1990 ; Shipulo et al. 2008 ). It has been recently
shown that fluorophores can be loaded with high yields into poly(ECA) (PECA)
nanoparticles prepared by anionic emulsion polymerization (Yordanov et al. 2009 ).
This aqueous emulsion polymerization procedure was adapted to the synthesis of
PACA nanospheres of PECA, poly( n butyl cyanoacrylate) (P n BCA), poly(hexyl
cyanoacrylate) (PHCA) and poly(octyl cyanoacrylate) (POCA) with a magnetic
core and loaded with Tegafur as the anticancer drug (Arias et al. 2008a ). This
method was scaled up to achieve production of clinical batches of PACA nanopar-
ticles loaded with doxorubicine and those of PACA nanoparticles loaded with
mitoxantrone evaluated in clinics for the treatment of hepatocellular carcinoma in
human ( BioAlliance Pharma 2009 ; Zhou et al. 2009 ).
P n BCA nanospheres were also prepared by miniemulsion and emulsion polymer-
ization using molecular or macromolecular surfactants (Maitre et al. 2000 ; Cauvin et al.
2002 ; Limouzin et al. 2003 ; Weiss et al. 2007 ) or by the nanoprecipitation technique
from the preformed polymer using pluronic F68 as a surfactant (He et al. 2008 ).
In order to increase the encapsulation yield of peptides into PACA nanoparticles,
a copolymerization approach was developed in combination with a microemulsion
process (Fig. 8 ). The peptide with the following sequence KAVYNFATM was
derived with an acryloyl group and copolymerized with ECA in water-in-oil (w/o)
microemulsion to yield stable peptide-loaded PECA nanoparticles of 250 nm in
average diameter (Liang et al. 2008 ). In this approach, the peptide loading was
twice-fold higher than that of with the unmodified peptide. In contrast, the same
copolymerization performed using a micellar template only conducted to unstable
aggregates.