Poly(Alkyl Cyanoacrylate) Nanosystems - Intracellular Delivery: Fundamentals and Applications - page 236

2007 ). Recently, poly( N -isopropylacrylamide) (PNIPAAm)/PECA composite hollow
particles were successfully prepared by an emulsification process, followed by
anionic polymerization of ECA and photopolymerization of N -isopropylacrylamide
(NIPAAm) (Lee et al. 2010 ). The shell layer of the composite hollow particle was
changed from semi-interpenetrating network to double shell layers by varying the
mass ratio of NIPAAm to ECA monomers.
The synthesis of nanocapsules from preformed PACA polymers (called interfa-
cial deposition) is also possible and consists of the addition of the polymer solu-
tion and a small amount of oil (which will constitute the oily core of the
nanocapsules), into an aqueous solution of surfactant. The oil-containing nanocap-
sules were formed instantaneously by deposition of the polymer at the oil/water
interface, which precipitates as a macromolecular shell (Barratt et al. 1994 ;
Brigger et al. 2003 ; Mayer 2005 ).
Miniemulsion polymerization was also employed to prepare monodisperse
DNA-containing, P n BCA nanocapsules by inverse miniemulsion polymerization
(Musyanovych and Landfester 2008 ). It was shown that the nature of the continuous
phase played the major role over the average diameter and the particle size distribution
whereas the monomer concentration governed the shell thickness and the nanocap-
sule morphology.

4.2 Second Generation: Surface Engineered and Stealth

Nanoparticles

In order to avoid quick accumulation of PACA nanoparticles into the liver and the
spleen due to adsorption of opsonins onto their surface, which triggers the recognition
of the mononuclear phagocyte system (MPS) by the macrophages, surface modified
nanoparticles were developed. In this view, the major breakthrough was the grafting
of PEG chains (the so-called PEGylation) (Stolnik et al. 1995 ; Storm et al. 1995 )
onto their surface which resulted in long-circulating drug delivery devices, also
termed “stealth” nanoparticles.
Although simple adsorption of surfactant has been reported to prepared surface-
modified PACA nanoparticles (Wilson et al. 2008 ; Kurakhmaeva et al. 2009 ), the
following will only focus on covalent linkage between the core of the NPs and its
coating.

4.2.1 Anionic and Zwitterionic Polymerization

The preparation of PACA nanospheres covered by PEG chains was achieved by
using methoxypoly(ethylene glycol) (MePEG) or PEG as both stabilizer and initiator
through zwitterionic emulsion polymerization of IBCA (Peracchia et al. 1997c, d ).
This led to PEG-coated PIBCA nanospheres where PEG chains exhibited different