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Microencapsulation of rifampicin: A technique to preserve the mechanical properties of bone cement
Pablo Sanz-Ruiz1,2, Esther Carbó-Laso1, Juan Carlos Del Real-Romero3
1Department of Traumatology and Orthopaedic Surgery, University General Hospital Gregorio Marañon, Doctor Esquerdo 46, 28007, Madrid, Spain.
Abstract:
Two-stage exchange with antibiotic-loaded bone cement spacers remains the gold standard for chronic periprosthetic joint infection (PJI). Rifampicin is highly efficient on stationary-phase staphylococci in biofilm; however, its addition to PMMA to manufacture spacers prevents polymerization and reduces mechanical properties. Isolation of rifampicin during polymerization by microencapsulation could allow manufacturing rifampicin-loaded bone cement maintaining elution and mechanical properties. Microcapsules of rifampicin with alginate, polyhydroxybutyratehydroxyvalerate (PHBV), ethylcellulose and stearic acid (SA) were synthesized. Alginate and PHBV microcapsules were added to bone cement and elution, compression, bending, hardness, setting time and microbiological tests were performed. Repeated measures ANOVA and Bonferroni post-hoc test were performed, considering a p < 0.05 as statistical significance. Bone cement specimens containing alginate microcapsules eluted more rifampicin than PHBV microcapsules or non-encapsulated rifampicin over time (p < 0.012). Microencapsulation of rifampicin allowed PMMA to preserve mechanical properties in compression and bending tests. Cement with alginate microcapsules showed similar behavior in hardness tests to control cement over the study period (73 ± 1.68HD ). PMMA with alginate microcapsules exhibited the largest zones of inhibition in microbiological tests. Statistically significant differences in mean diameters of zones of inhibition between PMMA loaded with alginate-rifampicin (p = 0.0001) and alginate-PHBV microcapsules (p = 0.0001) were detected. Rifampicin microencapsulation with alginate is the best choice to introduce rifampicin in PMMA preserving mechanical properties, setting time, elution, and antimicrobial properties. The main applicability of this study is the opportunity for obtaining rifampicin-loaded PMMA by microencapsulation of rifampicin in alginate microparticles, achieving high doses of rifampicin in infected tissues, increasing the successful of PJI treatment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:459-466, 2018.
Insights
Microencapsulating rifampicin in alginate preserves bone cement mechanical and elution properties for treating periprosthetic joint infections (PJI). This method enhances antibiotic delivery to infected tissues, improving PJI treatment success.
Area of Science:
- Biomaterials Science
- Orthopaedic Surgery
- Infectious Diseases
Background:
- Two-stage exchange with antibiotic-loaded bone cement spacers is the gold standard for chronic periprosthetic joint infection (PJI).
- Rifampicin is effective against staphylococci in biofilms but compromises bone cement polymerization and mechanical properties when directly added to polymethyl methacrylate (PMMA).
Purpose of the Study:
- To develop a method for incorporating rifampicin into PMMA bone cement while maintaining its mechanical and elution properties.
- To evaluate the efficacy of microencapsulated rifampicin in alginate for treating PJI.
Main Methods:
- Synthesized rifampicin microcapsules using alginate, polyhydroxybutyratehydroxyvalerate (PHBV), ethylcellulose, and stearic acid.
- Incorporated alginate and PHBV microcapsules into PMMA bone cement.
- Performed elution, compression, bending, hardness, setting time, and microbiological tests.
Main Results:
- Alginate microcapsules demonstrated significantly higher rifampicin elution over time compared to PHBV or non-encapsulated rifampicin.
- Microencapsulation preserved the mechanical properties (compression, bending, hardness) of PMMA bone cement.
- PMMA with alginate microcapsules exhibited the largest zones of inhibition in microbiological tests, indicating superior antimicrobial activity.
Conclusions:
- Rifampicin microencapsulation with alginate is optimal for PMMA, preserving mechanical, setting, elution, and antimicrobial properties.
- This approach enables high-dose rifampicin delivery to infected tissues, potentially increasing PJI treatment success.
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