Silica-Based Nanoparticles for Intracellular Drug Delivery - Intracellular Delivery: Fundamentals and Applications - page 347

erythromycin (Doadrio et al. 2006 ) and alendronate (Balas et al. 2006 ), using different
strategies to modify the control of drug release. Tamanoi et al demonstrated the release of
camptothecin, a hydrophobic anti-cancer drug, from MSN (Lu et al. 2007 ). The delivery
into malignant cells, growth inhibition and then cells death was confirmed. The enhanced
bioavailability of itraconazole, a model drug, was confirmed when included within the
silica porous matrix (Mellaerts et al. 2008 ). Tested in dogs and rabbits, the MSN material
can be considered as a promising carrier to perform oral availability for drugs with
extremely low water solubility.
MSN-based stimuli-responsive systems using a concept of gate-keeping were
first developed by V. S.-Y. Lin and his group (Slowing et al. 2008 ). This redox-
controlled drug delivery system is based on MSN capped with cadmium sulphide
(CdS) (Fig. 6 ). In this system, CdS was chemically attached to MSN through a disulfide
linker, which is chemically labile and that could be cleaved with various disul-
fide reducing agents, such as dithiothreitol (DTT) and mercaptoethanol (ME). The
working principle of the stimuli-controlled release drug/gene delivery system was
tested on imaging agents such as fluorescein, Texas Red or rhodamine B in order to
perform the conditions of guest molecules to be released under adapted gate-opening
trigger concentration and to demonstrate the performance of these systems. The
loading is usually in the order of hundreds milligrams of guest molecule per gram of
MSN. This type of drug delivery system with “zero premature release” performance
is particularly useful when the cargo to be delivered is toxic, like anti-cancer drugs.
These materials are potentially candidates for releasing drug/gene “at will”, i.e. to
control precisely the location and timing of the release of drug. Through this method,
the controlled release to live cells of vancomycin and adenosine triphosphate by
such CdS-MSN system was successfully demonstrated (Lai et al. 2003 ).
Fig. 6 Schematic illustration of the CdS-based gate-keeper strategies in mesoporous particles
(Reprinted from (Slowing et al. 2008 ), Copyright (2008), with permission from Elsevier)