Antibacterial efficacy of inhalable levofloxacin-loaded polymeric nanoparticles against E. coli biofilm cells: The effect of antibiotic release profile

Purpose: To investigate the effect of the antibiotic release profiles of levofloxacin-loaded polymeric nanoparticles on their antibacterial efficacy against E. coli biofilm cells. Methods: Three distinct antibiotic release profiles are produced by encapsulating levofloxacin in PCL and PLGA nanoparticles by nanoprecipitation and emulsification-solvent-evaporation methods. The antibacterial efficacy is examined over six days by time-dependent biofilm susceptibility testing that takes into account the effects of the biofilm age, antibiotic exposure history, and simulated drug removal. Results: Biofilm cells that survive the initial antibiotic exposure exhibit a higher antibiotic tolerance than fresh biofilm cells, where the lower the initial exposure, the higher the tolerance of the surviving biofilm cells. The lower antibiotic susceptibility of the surviving biofilm cells is transferred to their planktonic cell progeny, which can subsequently form new biofilm colonies having a higher antibiotic tolerance, hence exacerbating the infections. A biphasic extended release profile at an appropriate dose can inhibit the biofilm growth for four days, therefore reducing the dosing frequency. The importance of a high initial antibiotic exposure renders a slow release profile ineffective despite the same dosing amount. Conclusions: The antibiotic release profile has an equally significant influence on the biofilm eradication rate as the antibiotic dose.