Poly(Alkyl Cyanoacrylate) Nanosystems - Intracellular Delivery: Fundamentals and Applications - page 235

Fig. 8 Copolymerization mechanism of alkyl cyanoacrylate and acryloyl peptide

4.1.2 Nanocapsules

As opposed to nanospheres, PACA nanocapsules allowed a broader variety of
drugs to be encapsulated. Indeed, oil-containing nanocapsules will be able to
encapsulate hydrophobic drugs, whereas hydrophilic ones will be efficiently
encapsulated into water-containing nanocapsules. Basically, the shell of the nano-
capsule is formed by spontaneous anionic polymerization of alkyl cyanoacrylate
occurring at the interface between the dispersed and the continuous phase during
emulsion or microemulsion polymerization. The nature of the dispersed phase
involved in a heterogeneous polymerization process governs the nature of the
nanocapsules. Several studies reported the preparation of oil-containing PACA
nanocapsules (Fallouh et al. 1986 ; Gallardo et al. 1993 ; Wohlgemuth and Mayer
2003 ; Bogdan et al. 2008 ) and highlighted the importance of the diffusion behav-
ior of the organic solvent within the aqueous phase and the simultaneous precipita-
tion of the polymer at the oil/water interface (Fallouh et al. 1986 ; Gallardo et al.
1993 ). Average diameters usually observed for such nanocapsules range from 200
to 350 nm (even though a miniemulsion process (Altinbas et al. 2006 ) allowed
average diameters below 100 nm to be obtained) and are mainly governed by the
nature and the concentration of the monomer, the amount of surfactant and oil as
well as the speed of diffusion of the organic phase within the aqueous one. A
drawback usually encountered during the preparation of nanocapsules is a pollut-
ing population of nanospheres resulting from a partial polymerization in the
organic phase (Gallardo et al. 1993 ). This can be improved by an optimized etha-
nol/oil ratio (Gallardo et al. 1993 ; Aboubakar et al. 1999 ), the acidification of the
organic phase (Wohlgemuth and Mayer 2003 ) or the inhibition of the polymeriza-
tion in the organic phase by aprotic solvents (Puglisi et al. 1995 ).
Water-containing PACA nanocapsules were obtained by inverse (i.e., water-in-oil)
emulsion or microemulsion polymerization. Depending on the nature of the surfactant
and the starting system (emulsion or microemulsion), this process led to nanocap-
sules between 50 and 350 nm (Vranckx et al. 1996 ; Lambert et al. 2000 ;
Watnasirichaikul et al. 2002 ; Krauel et al. 2005 ; Hillaireau et al. 2007 ). If required,
a second step can be applied to transfer nanocapsules from an oil-dispersing
medium to a water-dispersing medium and consisted in a centrifugation step of the
nanocapsules onto an aqueous layer (Lambert et al. 2000 ; Hillaireau et al. 2006,