In vitro cell compatibility and antibacterial activity of microencapsulated doxycycline designed for improved localized therapy of septic arthritis.
Abstract: For the treatment of septic arthritis in large animals, the local application of antibiotics as a slow release system may be an appropriate means to reach high local bioactivity and low systemic side effects and drug residues. In this study, doxycycline microspheres were developed and tested in vitro for their drug-release properties, suitability for intra-articular application and antimicrobial activity. Methods: The development of a slow release system was achieved by microencapsulation of the drug into poly(lactide-co-glycolide) microspheres by a novel ultrasonic atomization method. Drug elution was evaluated from microspheres dispersed in elution medium at pre-defined time points by HPLC. Joint-tissue compatibility was tested on cultured bovine synoviocytes by evaluating the expression of pro-inflammatory cytokine mRNA and the production of nitric oxide (NO). Finally, the antimicrobial activity of the released antibiotic was assessed with gram-negative and gram-positive bacteria exposed to release medium sampled at days 1, 7 and 12 after microsphere suspension. Results: An adequate size of the microspheres, sufficient stabilization of doxycycline in aqueous environment and drug release (25 mg microspheres in 4 mL medium) above MIC for bacteria usually isolated in bovine and equine joints were obtained over 15 days. Although the cytokine mRNA expression reflected the excellent tissue compatibility, the results with NO yielded contradictory results. Antimicrobial tests of the release medium proved to match perfectly the activity of non-encapsulated, free doxycycline as reported in the literature. Conclusions: The newly developed doxycycline delivery system achieved the target specifications and is ready for in vivo testing.
Publication Date: 2008-01-03 PubMed ID: 18174200DOI: 10.1093/jac/dkm491Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates the development and testing of doxycycline microspheres for use in treating septic arthritis in large animals, such as cows and horses. The goal is to create a slow-release system that delivers the drug directly to the joint, which would improve the drug’s local effectiveness while minimizing systemic side effects and residues.
Research Methodology
- The researchers developed a slow-release system by encapsulating doxycycline, an antibiotic, in poly(lactide-co-glycolide) microspheres. This encapsulation was achieved through a new process of ultrasonic atomization.
- The release of the drug from the microspheres was then assessed over time by dispersing the spheres in an elution medium and measuring the amount of doxycycline in the medium at certain time points.
- They also tested the microspheres’ compatibility with joint tissue by culturing bovine synoviocytes, or joint-lining cells, and measuring the expression of pro-inflammatory cytokines and the production of nitric oxide.
- The researchers evaluated the antibacterial effectiveness of the released doxycycline by exposing common bacteria found in bovine and equine joints to the medium containing the released drug at 1, 7, and 12 days after suspension.
Results
- An adequate size for the microspheres was achieved, and they were able to stabilize doxycycline in an aqueous environment.
- Drug release from the microspheres was maintained above the bacteria’s minimum inhibitory concentration for over 15 days.
- While the expression of pro-inflammatory cytokines reflected excellent tissue compatibility, measuring nitric oxide production yielded inconsistent results, which may need further investigation.
- The antibacterial tests mirrored the activity of non-encapsulated, free doxycycline, demonstrating that the encapsulation did not impair the drug’s effectiveness.
Conclusions
The new microencapsulated doxycycline delivery system met the project’s aims and is now ready for testing in live animals. The ability to provide a slow-release, localized antibiotic treatment may greatly improve the outcomes for large animals suffering from septic arthritis. Further research will explore this potential and provide vital data on side-effect profiles and other clinically relevant parameters.
Cite This Article
APA
Haerdi-Landerer MC, Suter MM, Steiner A, Wittenbrink MM, Pickl A, Gander BA.
(2008).
In vitro cell compatibility and antibacterial activity of microencapsulated doxycycline designed for improved localized therapy of septic arthritis.
J Antimicrob Chemother, 61(2), 332-340.
https://doi.org/10.1093/jac/dkm491 Publication
Researcher Affiliations
- AO Research Institute, 7270 Davos-Platz, Switzerland. christina-haerdi@ethz.ch
MeSH Terms
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / chemistry
- Arthritis, Infectious / drug therapy
- Arthritis, Infectious / pathology
- Cattle
- Cells, Cultured
- Doxycycline / administration & dosage
- Doxycycline / chemistry
- Drug Compounding / methods
- Drug Delivery Systems / methods
- Microspheres
- Particle Size
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