Mucolytic and antibiotic combination therapy using silica-based nanocarriers to eradicate <i>Escherichia coli</i> biofilms

This research provides new insights into the treatment of <i>E. coli</i> biofilm-related infections through the design of new antimicrobial nanoformulations based on mesoporous silica nanoparticles (MSNs) for mucolytic and antibiotic combination therapy against <i>E. coli</i> biofilms. The development of nanosystems with well-defined compartments to house and sequentially deliver different antimicrobial agents was carried out. A relatively simple and direct straightforward approach was carried out, consisting of loading MSNs with levofloxacin (LVX) by an impregnation method followed by external coating with a gelatin shell embedding a mixture of <i>N</i>-acetylcysteine (AC) plus LVX. Thus, the release of the mucolytic agent, AC, at the earliest stage causes disaggregation of the outer mucopolysaccharide layer of the mature <i>E. coli</i> biofilm, as confirmed by confocal laser scanning microscopy studies. This biofilm disruption effect facilitates the antimicrobial action of LVX, which is released in a more sustained manner over longer periods of time than AC, achieving a remarkable reduction (<i>ca.</i> 99.8%) of mature <i>E. coli</i> biofilms. These results are supported by the combined effect of AC and LVX strategically combined in the same nanocarrier. Preliminary <i>in vitro</i> studies with preosteoblastic cells point to the good biocompatibility of these nanosystems.