The New Strategy for Studying Drug-Delivery Systems with Prolonged Release: Seven-Day In Vitro Antibacterial Action

The new method of antibacterial-drug-activity investigation in vitro is proposed as a powerful strategy for understanding how carriers affect drug action during long periods (7 days). In this paper, we observed fluoroquinolone moxifloxacin (MF) antibacterial-efficiency in non-covalent complexes, with the sulfobutyl ether derivative of β-cyclodextrin (SCD) and its polymer (SCDpol). We conducted in vitro studies on two Escherichia coli strains that differed in surface morphology. It was found that MF loses its antibacterial action after 3-4 days in liquid media, whereas the inclusion of the drug in SCD led to the increase of MF antibacterial activity by up to 1.4 times within 1-5 days of the experiment. In the case of MF-SCDpol, we observed a 12-fold increase in the MF action, and a tendency to prolonged antibacterial activity. We visualized this phenomenon (the state of bacteria, cell membrane, and surface morphology) during MF and MF-carrier exposure by TEM. SCD and SCDpol did not change the drug's mechanism of action. Particle adsorption on cells was the crucial factor for determining the observed effects. The proteinaceous fimbriae on the bacteria surface gave a 2-fold increase of the drug carrier adsorption, hence the strains with fimbriae are more preferable for the proposed treatment. Furthermore, the approach to visualize the CD polymer adsorption on bacteria via TEM is suggested. We hope that the proposed comprehensive method will be useful for the studies of drug-delivery systems to uncover long-term antibacterial action.