  Mesoporous silica nanoparticles (MSNs) are promising drug nanocarriers for
infection treatment. Many investigations have focused on evaluating the
capacity of MSNs to encapsulate antibiotics and release them in a controlled
fashion. However, little attention has been paid to determine the antibiotic
doses released from these nanosystems that are effective against biofilm during
the entire release time. Herein, we report a systematic and quantitative study
of the direct effect of the antibiotic-cargo released from MSNs on
Gram-positive and Gram-negative bacterial biofilms. Levofloxacin (LVX),
gentamicin (GM) and rifampin (RIF) were separately loaded into pure-silica and
amino-modified MSNs. This accounts for the versatility of these nanosystems
since they were able to load and release different antibiotic molecules of
diverse chemical nature. Biological activity curves of the released antibiotic
were determined for both bacterial strains, which allowed to calculate the
active doses that are effective against bacterial biofilms. Furthermore, in
vitro biocompatibility assays on osteoblast-like cells were carried out at
different periods of times. Albeit a slight decrease in cell viability was
observed at the very initial stage, due to the initial burst antibiotic
release, the biocompatibility of these nanosystems is evidenced since a
recovery of cell viability was achieved after 72 h of assay. Biological
activity curves for GM released from MSNs exhibited sustained patterns and
antibiotic doses in the 2-6 {\mu}g/mL range up to 100 h, which were not enough
to eradicate biofilm. In the case of LVX and RIF first-order kinetics featuring
an initial burst effect followed by a sustained release above the MIC up to 96
h were observed. Such doses reduced by 99.9% bacterial biofilm and remained
active up to 72 h with no emergence of bacterial resistance.
