Microencapsulation of rifampicin: a technique to preserve the mechanical properties of bone cement

P. Sanz-Ruiz, E. Carbó-Laso, J.C. del Real-Romero, F. Arán-Ais, Y. Ballesteros, E. Paz, M.M. Sánchez-Navarro, M.A. Pérez-Limiñana, J. Vaquero-Martín

Journal of Orthopaedic Research Vol. 36, nº. 1, pp. 459 - 466

Summary:
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.

Keywords: Rifampicin-loaded bone cement; rifampicin microencapsulation; bone cement spacers; periprosthetic infection

JCR Impact Factor and WoS quartile: 3,043 - Q1 (2018); 2,800 - Q2 (2022)

DOI reference: https://doi.org/10.1002/jor.23614

Published on paper: January 2018.

Published on-line: May 2017.

Citation:
P. Sanz-Ruiz, E. Carbó-Laso, J.C. del Real-Romero, F. Arán-Ais, Y. Ballesteros, E. Paz, M.M. Sánchez-Navarro, M.A. Pérez-Limiñana, J. Vaquero-Martín Microencapsulation of rifampicin: a technique to preserve the mechanical properties of bone cement. Journal of Orthopaedic Research. Vol. 36, nº. 1, pp. 459 - 466, January 2018. [Online: May 2017]