Functional Mesoporous Silica Nanoparticles with a Core-Shell Structure for Controllable Drug Delivery - Advanced Bioactive Inorganic Materials for Bone Regeneration and Drug Delivery - page 53

hydrothermal treatment (Route B). Thus, monodisperse HMS nanoparticles
with tunable particle/pore sizes can be obtained by selectively removing the
solid silica cores (Figure 3.2) (Chen, Chen, Guo, et al. 2010).
3.2.2 Functional Hollow Mesoporous Silica
Nanoparticles for Drug Delivery
Many studies have demonstrated that HMS nanoparticles exhibit higher
drug-loading capacity compared to conventional mesoporous silica nanopar-
ticles. For example, Zhao et al. (2009) have reported that the maximum ibu-
profen (IBU) loading capacity of HMS nanoparticles (726 mg/g) is much
higher than the reported maximum IBU loading capacity of MCM-41 (358
mg/g), although the surface area and pore volume of HMS nanoparticles
(455 m 2 /g, 0.59 cm 3 /g) are much lower than those of MCM-41 (1152 m 2 /g ,
0.99 cm 3 /g). However, pure HMS nanoparticles as carriers for drug delivery
only show the sustained drug release behavior and are difficult to control the
drug release rate (the pore diameter and pore structure type determine the
drug release rate) (Vallet-Regí et al. 2001; Andersson et al. 2004; Izquierdo-
Barba et al. 2009).
Recently, many efforts have been made to improve the drug delivery prop-
erties by functionalizing HMS nanoparticles (Zhu, Shi, Li, et al. 2005; Zhu
and Shi 2007; Zhang et al. 2010). On the one hand, for drug molecules loading
in HMS nanoparticles, some drug molecules are located in the hollow cores,
and others are loaded in the mesoporous channels and on the surfaces of
mesoporous walls through weak interactions, such as hydrogen bonding,
physical adsorption, and electrostatic interactions. Therefore, functionaliza-
tion of the mesoporous shells with appropriate groups, presenting attractive
interactions with drug molecules and slightly turning the pore diameter,
may provide an effective control on the drug loading and release rate. Zhu,
Shi, Li, et al. (2005) functionalized hollow mesoporous silica spheres with
cubic pore network (HMSC) with 3-aminopropyltriethoxysilane (N-TES),
3-(2-aminoethylamino)- propyltrimethoxysilane (NN-TES), and (3-trime-
thoxysilylpropyl)diethylenetriamine (NNN-TES) at different levels by a sim-
ple one-step method and postmodification process. With the increase of the
amount of functional groups introduced, the IBU drug release rate becomes
lower. At the same amount of functional groups, the IBU drug release rate
follows the order: NNN-HMSC < NN-HMSC < NHMSC. Obviously, func-
tionalization of HMS nanoparticles with appropriate groups can control the
drug release rate but still exhibit the sustained release behavior.
On the other hand, compared to the sustained release system, the stimuli
responsive controlled release system can achieve a site selective controlled
release pattern, which can improve the therapeutic efficacy. Zhu and Shi
(2007) proposed a strategy to functionalize HMS nanoparticles with the
pH-responsive polyelectrolyte multilayers [the polyelectrolyte pair, sodium
poly(styrene sulfonate) (PSS), and polycation poly(allylamine hydrochloride)