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Effectiveness of ciprofloxacin microspheres in eradicating bacterial biofilm
G Owusu-Ababio1, J Rogers, H Anwar
1College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA. ababiog@mail.firn.edu
Abstract:
The treatment of cultures of planktonic cells and aged biofilm cells of P. aeruginosa and S. aureus with ciprofloxacin (CFX) microspheres of poly(l-lactic acid) (PLA) has been investigated using a modified, open in vitro chemostat system. The kinetics of release of CFX as a function of drug loading and the dose of microspheres were correlated with the rate and extent of killing and eradication of the planktonic cells and biofilm cells cultured on pieces of silicone tubing in the chemostat, respectively. At 71% w/w drug loading, a minimum dose of 7 mg of CFX in microspheres was required to sustain CFX concentration for about 10 h above the minimum inhibitory concentration (MIC) in order to completely eradicate the cells of either bacteria. In contrast, peak concentrations obtained from an equivalent dose of free CFX decreased to low values within 30 min and the bacteria cells were not eradicated. Lower microsphere loadings of CFX were ineffective at the same dose. Thus, this study has identified the formulation requirements for PLA microspheres to sustain CFX concentrations above the MIC for several days in order to eradicate bacteria, particularly aged biofilm cells, in the open chemostat in which the drug is being continually diluted, or similarly at a site of administration, for example, in the peritoneal cavity.
Insights
Poly(l-lactic acid) microspheres effectively eradicated P. aeruginosa and S. aureus biofilms by sustaining ciprofloxacin concentrations above the minimum inhibitory concentration for extended periods.
Area of Science:
- Biomaterials Science
- Microbiology
- Pharmacology
Background:
- Biofilm infections pose significant challenges due to inherent resistance to antibiotics.
- Conventional antibiotic delivery often fails to maintain therapeutic concentrations, especially in dynamic environments.
- Poly(l-lactic acid) (PLA) microspheres offer a potential platform for sustained drug delivery.
Purpose of the Study:
- To investigate the efficacy of ciprofloxacin (CFX)-loaded PLA microspheres against planktonic and biofilm cells of P. aeruginosa and S. aureus.
- To correlate CFX release kinetics from microspheres with bacterial eradication rates.
- To determine formulation requirements for effective biofilm eradication using PLA microspheres.
Main Methods:
- Utilized a modified, open in vitro chemostat system to culture bacterial cells.
- Treated planktonic and aged biofilm cells with CFX-loaded PLA microspheres.
- Varied drug loading and microsphere dosage to assess CFX release and antibacterial activity.
- Monitored CFX concentrations and bacterial viability over time.
Main Results:
- A minimum dose of 7 mg of CFX in microspheres (71% w/w loading) sustained concentrations above the minimum inhibitory concentration (MIC) for approximately 10 hours, achieving complete eradication.
- Free CFX, even at equivalent doses, failed to eradicate bacteria due to rapid concentration decline within 30 minutes.
- Lower microsphere drug loadings were ineffective at the same dosage.
- Sustained CFX release from PLA microspheres demonstrated superior efficacy against aged biofilm cells compared to free CFX.
Conclusions:
- PLA microspheres can be formulated to sustain ciprofloxacin concentrations above the MIC for extended periods, crucial for eradicating challenging bacterial infections.
- This approach is particularly effective against aged bacterial biofilms, which are notoriously difficult to treat.
- The findings provide essential formulation guidelines for developing effective PLA microsphere-based antibiotic delivery systems for localized infections or environments with continuous dilution.
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