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Antibacterial Efficacy of Inhalable Levofloxacin-Loaded Polymeric Nanoparticles Against E. coli Biofilm Cells: The Effect of Antibiotic Release Profile

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ABSTRACT

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.

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Abbreviations

CFU:

colony forming unit

COPD:

chronic obstructive pulmonary disease

DCM:

dichloromethane

DPI:

dry powder inhaler

EPS:

extracellular polymeric substance

ESE:

emulsification-solvent-evaporation

LEV:

levofloxacin

MBIC:

minimum biofilm inhibitory concentration

MHB:

mueller Hinton Broth

MIC:

minimum inhibitory concentration

NP:

nanoparticles

NPC:

nanoprecipitation

OD:

optical density

PBS:

phosphate buffer saline

PCL:

poly(caprolactone)

PLGA:

poly(DL-lactide-co-glycolide)

PVA:

poly (vinyl alcohol)

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ACKNOWLEDGEMENTS

Financial support from Nanyang Technological University’s Start-Up Grant (Grant No. SUG 8/07) is gratefully acknowledged. The authors would like to thank Dr. Qi Xiaobao for his contributions in the antibiotic susceptibility testing.

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Authors and Affiliations

  1. School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637459, Singapore

    Wean Sin Cheow, Matthew Wook Chang & Kunn Hadinoto

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  1. Wean Sin Cheow
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  2. Matthew Wook Chang
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  3. Kunn Hadinoto
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Correspondence to Kunn Hadinoto.

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Cheow, W.S., Chang, M.W. & Hadinoto, K. Antibacterial Efficacy of Inhalable Levofloxacin-Loaded Polymeric Nanoparticles Against E. coli Biofilm Cells: The Effect of Antibiotic Release Profile. Pharm Res 27, 1597–1609 (2010). https://doi.org/10.1007/s11095-010-0142-6

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