Mucolytic and antibiotic combination therapy using silica-based nanocarriers to eradicate Escherichia coli biofilms

Abstract

This research provides new insights into the treatment of E. coli biofilm-related infections through the design of new antimicrobial nanoformulations based on mesoporous silica nanoparticles (MSNs) for mucolytic and antibiotic combination therapy against E. coli 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 N-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 E. coli 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 (ca. 99.8%) of mature E. coli biofilms. These results are supported by the combined effect of AC and LVX strategically combined in the same nanocarrier. Preliminary in vitro studies with preosteoblastic cells point to the good biocompatibility of these nanosystems.