Silica-Based Nanoparticles for Intracellular Drug Delivery - Intracellular Delivery: Fundamentals and Applications - page 336

by temperature and by specific surface area (either surface/volume ratio for particles
or porosity for bulk materials) (Rimer et al. 2007 ).
The presence of additives in the reaction media may have several impacts on
these processes. Inorganic salts tend to reduce the stability of silica particle sols due
to surface charge screening, decrease solubility of silica and increase dissolution
rate (Wallace et al. 2010 ). Polymers may favor or limit silica condensation as func-
tion of their charge and concentration. They can also coat the surface of silica
particles, decreasing the availability of silanol groups and therefore decreasing their
dissolution rate.

2.2 Strategies for Silica Nanoparticle Formation

2.2.1 Pure Silica Nanoparticle Formation

Nowadays, the so-called Stöber process is undoubtedly the most popular route to
obtain colloidal silica (Stöber et al. 1968 ). It is based on the growth of silica nano-
particles from silicon alkoxides (mainly tetraethoxysilane, TEOS) in basic media
(ammonia solution) in the presence of an alcohol as a co-solvent. The basic condi-
tions are required to obtain fast condensation and particle stabilization. The alcohol
favors the initial solubilization of the silicon alkoxide precursor and probably limits
particle growth by increasing the interfacial energy. Despite its apparent simplicity,
the Stöber process requires a careful control of process parameters (volume, stirring,
mixing rate) to get access to monodisperse populations, especially in the small size
domain (i.e. below ca. 50 nm). Therefore many modifications of the initial procedure
are available to improve the size distribution (Bogush et al. 1988 ; Rao et al. 2005 ).
For instance, a seed-growth approach was developed that starts from well-defined
small colloids that are further grown in a TEOS/ammonia solution (Chang et al.
2005 ) (Fig. 1 ). A recent report also shows that soluble silicates can be used to form
silica nanoparticles by simple ethanol addition (Jung et al. 2010 ). This emphasizes
that the main parameter controlling the particle size is the interfacial energy. Thus,
it is not surprising that silica nanoparticles have also been grown within emulsion
systems in the presence of surfactants (Arriagada and Osseo-Asare 1995 ; Gan et al.
1996 ). Finally, silica particles can also be obtained using spray-drying techniques
(Iskandar et al. 2003 ) but this approach has been mainly applied to hybrid and
porous nanomaterials, as described below (Baccile et al. 2003 )

2.2.2 Hybrid Silica Nanoparticle Formation

A first approach to convert pure silica nanoparticles into hybrid nanomaterials is
through the grafting of organic functions using organosilanes. A wide variety of these
silanes are commercially available, from hydrocarbon to amine- or thiol-terminated
chains. Although this approach has been extensively used (see Sect. 3 ), the precise
structure of the resulting surface is far from being understood (de Monredon-Senani