Biomedical Engineering Reference
In-Depth Information
A series of micro and mesoporous silica matrices varying in pore size, pore connectivity, and
pore geometry were prepared, and their drug loading and release behaviors as carriers were investi-
gated under
in vitro
conditions [19]. Ibuprofen (IBU) was used as a model drug. The loading degree
was related to both the surface area and the pore size of the silica matrix. The drug release process
could be described as a diffusion-controlled process. The nanostructured silicas that were studied
displayed a high degree of drug loading. Depending on the host material, a controlled drug release
could be provided for time periods varying from hours to weeks.
Compared with the sustained release system, the stimuli-responsive controlled-release system
can achieve a site-selective, controlled release behavior, which can improve the therapeutic effi cacy.
Till date, only a few reports have been published on stimuli-responsive controlled drug release from
mesoporous silica MCM-41 [20,21]. Fujiwara and coworkers realized the photo-controlled revers-
ible release of drug molecules from coumarin-modifi ed MCM-41 [20]. Lin et al. [21] reported the
synthesis of a MCM-41 mesoporous silica stimuli-responsive controlled drug release system, which
consisted of 2-(propyldisulfanyl) ethylamine functionalized mesoporous silica nanospheres (MSNs)
with an average particle size of 200 nm and an average pore diameter of 2.3 nm. The mesopores
of the MSNs were used as reservoirs to soak up aqueous solutions of various pharmaceutical drug
molecules and neurotransmitters such as vancomycin and adenosine triphosphate (ATP). The open-
ings of the mesopores of the drug/neurotransmitter-loaded MSNs were capped
in situ
by covalently
bonding between the pore surface-bound 2-(propyldisulfanyl) ethylamine functional groups and
water-soluble mercaptoacetic acid-derivatized cadmium sulfi de (CdS) nanocrystals [22] using a
reported amidation reaction [23]. The resulting disulfi de linkages between the MSNs and the CdS
nanoparticles were chemically labile in nature and could be cleaved with various disulfi de-reducing
agents such as dithiothreitol (DTT) and mercaptoethanol (ME). The release of the CdS nanoparticle
caps from the drug/neurotransmitter-loaded MSNs were regulated by introducing various amounts
of release triggers. The researchers investigated the stimuli-responsive release profi les, and the
delivery effi ciency of vancomycin and the ATP encapsulated inside the CdS-capped MSN system.
The N
2
adsorption/desorption isotherms revealed a BET isotherm typical of MCM-41 structure
(type IV) with a surface area of 941.0 m
2
/g and a narrow pore size distribution (average pore diam-
eter of 2.3 nm). In this delivery system, the drug molecules were encapsulated inside the porous
framework of the MSN not by adsorption or sol-gel type of entrapment but by capping the open-
ings of the mesoporous channels with size-defi ned CdS nanoparticles to physically block the drugs/
neurotransmitters of certain sizes from leaching out.
The CdS-capped MSN drug/neurotransmitter delivery system showed less than 1.0% of drug
release in 10 mM PBS buffer solutions (pH 7.4) over a period of 12 h (Figure 9.2a), implying a
good capping effi ciency of the CdS nanoparticles for encapsulation of the vancomycin and ATP
molecules [21]. A rapid release of the mesopore-entrapped drug/neurotransmitter was triggered by
the addition of disulfi de-reducing molecules such as DTT to the aqueous suspension of CdS-capped
MSNs. Within 24 h, 85% of the total release was observed. It is very interesting that the release
rates of vancomycin and ATP showed similar kinetic profi les, indicating the lack of interaction
between these released molecules and the mesoporous silica matrix. However, 53.8% of the encap-
sulated vancomycin was released after 3 days of the DTT-induced uncapping of the mesopores,
while only 28.2% of the entrapped ATP molecules were able to diffuse away. Such a signifi cant
difference in the release percentage of vancomycin and ATP implied that ATP molecules were more
strongly physisorbed to the organically functionalized mesoporous channels than the vancomycin
molecules. Furthermore, in both vancomycin and ATP cases, the amount of drug release after 24 h
of the addition of DTT showed similar DTT concentration dependencies (Figure 9.2b), indicating
that the release rate was dictated by the rate of removing the CdS caps.
Hollow mesoporous silica spheres are promising candidates as drug carriers. Shi et al. [24]
prepared hollow mesoporous silica spheres to enhance the loading capacity for the drugs. These
researchers investigated the aspirin storage capacity and release properties of these spheres. The
experiments showed that hollow mesoporous silica spheres could store signifi cantly more aspirin
