Poly(Alkyl Cyanoacrylate) Nanosystems - Intracellular Delivery: Fundamentals and Applications - page 233

Fig. 6 Synthesis of three-arm star cyanoacrylate-telechelic polyisobutylene (PIB-CA) 3

4 Poly(Alkyl Cyanoacrylate) Nanoparticles

Another important application of PACA is related to the field of drug delivery due
to their ability to form submicronic, biodegradable nanoparticles (Couvreur and
Vauthier 1991 ), although PACA-based microparticles have also been reported (Lee
et al. 2009 ; Li et al. 2009 ). Nanoparticle is a collective term which gathers different
types of colloidal objects: (i) nanospheres, a matrix-type system constituted by the
polymer in which the drug is homogeneously dispersed and (ii) nanocapsules,
which are vesicular systems in which the drug is solubilized in a liquid core (either
water or oil) surrounded by a thin polymer layer (Fig. 7 ) (Vauthier et al. 2003 ).

4.1 First Generation of Nanoparticles

4.1.1 Nanospheres

The first example in this field was reported in 1979 and consisted in a very simple
process to generate in situ MCA or ECA nanospheres via the polymerization of the
monomer into an acidic aqueous solution (2 < pH < 3) containing a nonionic or a
macromolecular surfactant (Couvreur et al. 1979 ). This synthetic route was applied
to various cyanoacrylate monomers and appeared to be a method of choice to pre-
pare PACA nanoparticles for drug delivery purposes (Sullivan and Birkinshaw
2004 ; Arias et al. 2007, 2008b ; Kisich et al. 2007 ; Kusonwiriyawong et al. 2008 ;
Maksimenko et al. 2008 ; Wilson et al. 2008 ; Hekmatara et al. 2009 ; Kurakhmaeva
et al. 2009 ). Numerous studies have also shown that macromolecular and colloidal
characteristics of the resulting nanospheres can be easily modified, simply by play-
ing on experimental parameters such as the nature and the concentration of the
monomer and the surfactant, the pH, the polymerization temperature, or the con-
centration of the inhibitor (El-Egakey et al. 1983 ; Douglas et al. 1984 ; Vansnick
et al. 1985 ; Seijo et al. 1990 ; Lescure et al. 1992 ; Yang et al. 2000 ; Dossi et al.