Silica-Based Nanoparticles for Intracellular Drug Delivery - Intracellular Delivery: Fundamentals and Applications - page 356

5 Conclusions

Taken together, this large amount of data and achievements suggest that
silica-based nanoparticles are promising candidates for intracellular drug
delivery. Their main advantages are the control of particle size and porosity as
well as the very versatile functionalization chemistry. Their main drawback is
clearly related to their biocompatibility but this term covers several aspects that
deserve to be discussed. First, it worth underlining that, like all other materials,
silica may coexist in several forms: colloidal, polymer and monomer of decreasing
size but of increasing reactivity. Second, several in vivo environments should
be distinguished: body fluids, cell membrane and intracellular space. Most
available data concern silica in the colloidal state in body fluids and at the
vicinity of cell membrane. In all these situations, it was suggested that a suit-
able surface functionalization allowed the decrease of the detrimental effect of
the silica particle. Considering colloidal silica within cells, there is a strong
lack of relevant information. In particular, to our knowledge, no long-term studies
of the fate of internalized particles are available. Turning our attention to solu-
ble forms of silica, only one paper has addressed the influence of silicic acids
on cells, and only in vitro (Linthicum 2001 ). This study indicated that these
species could be internalized, leading to intracellular damage. It can therefore
be suggested that these two fundamental aspects deserve to be studied in more
details.
From a practical point of view, it is also necessary to consider several factors.
First, the problem of colloidal stability is an important issue both during storage
but also when sterilization is to be undertaken. For instance, it is worth noting
that commercial solutions of silica nanoparticles contain stabilizers that may not
be fully compatible with in vivo applications. From an economical perspective,
the large-scale production of plain silica nanoparticles, as such or with simple
organic coatings is already existing. However, to our knowledge, this is not true
for mesoporous particles. Considering further functionalization of these carriers,
it is worth mentioning that organosilanes are quite expensive and that most
promising multifunctional particles involve several synthetic steps that may not
be easy to scale-up. Overall, it implies an extensive adaptation of the silica
industry to biomedical constraints. Such an adaptation will be triggered only if
(i) silica-based particles demonstrate strong benefits compared to more tradi-
tional (bio)-organic nanoparticles and (ii) a better understanding of their in vivo
behavior is gained.
Interestingly, recent bibliographic data suggest that most reports in this area
concern the elaboration of silica-based novel carriers (> 500 papers in the 2009-
2010 period from Web of Science ® ) whereas biological evaluations of silica parti-
cles are still scarce (ca. 60 papers over the same period). A better balance between
these two approaches must now be reached, especially through the development of
a true “biochemistry” of silica.