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Antibiotic microspheres: preliminary testing for potential treatment of osteomyelitis
Catherine G Ambrose1, Gloria R Gogola, Terry A Clyburn
1Department of Orthopaedics, University of Texas Health Science Center at Houston, Houston, TX, USA.
Abstract:
Osteomyelitis is a difficult problem for orthopaedic surgeons. The current standard of treatment requires high doses of antibiotic to be administered parenterally, which can damage vital organs. A local drug delivery system, which targets only the infected tissues, would eliminate some of the complications associated with extended courses of parenteral antibiotic treatment. In the current study, biodegradable microspheres were manufactured from a high molecular weight copolymer of 50% lactic and 50% glycolic acid and the antibiotic tobramycin. Various formulations of microspheres were tested for in vitro elution characteristics to determine the optimum formulation for linear release of antibiotic for at least 4 weeks. The optimal formulation then was implanted into a pouch created in the quadriceps muscle of mice to evaluate the in vivo elution of the antibiotic and the inflammatory response elicited by the microspheres. Results indicate that a sustained linear release of antibiotic from the microspheres is possible for a period of at least 4 weeks and that the inflammatory response was within levels required for the microspheres to be considered biocompatible.
Insights
Biodegradable microspheres deliver tobramycin locally for osteomyelitis treatment. This approach offers sustained antibiotic release for over 4 weeks, reducing parenteral antibiotic risks.
Area of Science:
- Biomaterials Science
- Orthopaedic Surgery
- Pharmacology
Background:
- Osteomyelitis presents significant challenges in orthopaedic surgery.
- Current treatments involve high-dose parenteral antibiotics, risking organ damage.
- Local drug delivery systems offer a targeted alternative to systemic administration.
Purpose of the Study:
- To develop and evaluate biodegradable microspheres for sustained local delivery of tobramycin.
- To optimize microsphere formulations for linear antibiotic release over at least 4 weeks.
- To assess the in vivo elution and biocompatibility of the microspheres.
Main Methods:
- Biodegradable microspheres were fabricated using a 50% lactic-50% glycolic acid copolymer and tobramycin.
- In vitro elution studies were performed to identify optimal formulations for linear release.
- In vivo studies in mice evaluated antibiotic elution and inflammatory response after implantation.
Main Results:
- Microsphere formulations demonstrated sustained, linear release of tobramycin for over 4 weeks in vitro.
- In vivo implantation showed continued antibiotic elution and a biocompatible inflammatory response.
- The microspheres proved suitable for local, sustained drug delivery.
Conclusions:
- Biodegradable microspheres offer a promising local drug delivery system for osteomyelitis.
- This method allows for prolonged, targeted tobramycin release, potentially mitigating systemic toxicity.
- The developed microspheres are biocompatible and suitable for orthopaedic applications.
