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Elution of metronidazole and gentamicin from polymethylmethacrylate beads
Jose R Ramos1, Rick D Howard, R Scott Pleasant
1Department of Large Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA.
Objective:
To characterize the elution and bioactivity of metronidazole and gentamicin sulfate polymerized, individually and in combination, with polymethylmethacrylate (PMMA).
Study Design:
In vitro experimental study.
Methods:
PMMA beads containing metronidazole (3 concentrations), gentamicin sulfate, or metronidazole and gentamicin sulfate were immersed in 5 mL of phosphate-buffered saline in triplicate. Eluent was replaced at specified time intervals for 1 or 21 days, and antibiotic concentrations were measured by high-performance liquid chromatography. Changes in antibiotic bioactivity attributable to polymerization or copolymerization of the antibiotics with PMMA, ethylene oxide sterilization, and storage of AIPMMA beads containing metronidazole were evaluated.
Results:
Antibiotic elution patterns were similar for all groups. Day 1 elution for groups containing metronidazole or gentamicin individually represented a mean 63%-66% and 79%, respectively, of the 21-day total. Approximately 50% of the day 1 elution occurred during the first hour. The elution of metronidazole was dose dependent. The elution of metronidazole (day 3-21) and gentamicin (all days) was significantly greater when metronidazole and gentamicin were combined (P <.05). The addition of metronidazole delayed polymerization of PMMA. Neither polymerization nor copolymerization of metronidazole and gentamicin with PMMA, gas sterilization, or 2-month storage of beads containing metronidazole significantly affected antimicrobial bioactivity.
Conclusions:
Metronidazole elution from PMMA was dose dependent. Copolymerization of metronidazole and gentamicin sulfate in PMMA resulted in increased rates of elution. Intraoperative preparation of metronidazole-impregnated PMMA beads is not practical, but sterilization and storage for 2 months should not affect efficacy.
Clinical Relevance:
The local delivery of biologically active metronidazole and gentamicin by elution from PMMA is feasible.
Insights
Local delivery of metronidazole and gentamicin from polymethylmethacrylate (PMMA) beads is feasible. Elution rates increased when combined, and sterilization/storage did not impact bioactivity, supporting clinical use.
Area of Science:
- Biomaterials Science
- Pharmacology
- Infectious Diseases
Background:
- Polymethylmethacrylate (PMMA) is widely used for bone cement.
- Local antibiotic delivery aims to achieve high concentrations at the infection site while minimizing systemic toxicity.
- Metronidazole and gentamicin sulfate are common antibiotics used in orthopedic surgery.
Purpose of the Study:
- To characterize the elution kinetics and bioactivity of metronidazole and gentamicin sulfate when polymerized with PMMA.
- To evaluate the impact of combination therapy and sterilization on antibiotic release and efficacy.
Main Methods:
- In vitro study using PMMA beads containing metronidazole, gentamicin sulfate, or both.
- Antibiotic concentrations in eluent were measured over 21 days using high-performance liquid chromatography (HPLC).
- Antibiotic bioactivity was assessed after polymerization, sterilization, and storage.
Main Results:
- Elution patterns were similar across groups, with significant early release (63-79% on day 1).
- Metronidazole elution was dose-dependent and increased when combined with gentamicin.
- Polymerization, sterilization, and storage did not significantly affect the antimicrobial bioactivity of the antibiotics.
Conclusions:
- Local delivery of bioactive metronidazole and gentamicin via PMMA elution is feasible.
- Combined metronidazole and gentamicin elution from PMMA showed increased release rates.
- PMMA beads offer a viable method for localized antibiotic delivery in clinical settings.