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

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 ± 1.68H ). 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.

Composite scaffold obtained by electro-hydrodynamic technique for infection prevention and treatment in bone repair

“…Rifampicin (RFP) is effective against staphylococcal infections and efficient for treatment at any bacterial growth stage (i.e. exponential, stationary, intracellular) (Frippiat et al, 2004;Sanz-Ruiz et al, 2017;Trampuz and Widmer, 2006). Furthermore, RFP is also one of the most effective first-line drugs for the treatment of tuberculosis and its bone-related effects (i.e.…”

A Novel Antimicrobial Peptide Scyreprocin From Mud Crab Scylla paramamosain Showing Potent Antifungal and Anti-biofilm Activity

“…Most antifungal drugs only effectively inhibit planktonic fungal cells during the exponential growth phase but have little effect on biofilms. Currently used antibiotics, including gentamicin (Scott and Higham, 2003), rifampicin (Sanz-Ruiz et al, 2018), and clindamycin (Neut et al, 2005;Ooi et al, 2017), have been applied on devices to cope with medical device HAIs, but the consequent emergence of antibiotic-resistance bacteria raise more questions (Thornes et al, 2002). Other antimicrobial agents, such as metals (Antonelli et al, 2012) and bacteriophages (Lu and Koeris, 2011), have been tested for their ability to remove biofilm.…”

Radical scavenging of poly(methyl methacrylate) bone cement by rifampin and clinically relevant properties of the rifampin-loaded cement

“…One approach is the encapsulation of rifampin before it is mixed with the cement. Sanz-Ruiz et al 33 encapsulated rifampin and reported effective elution of the antibiotic while preserving the mechanical properties of PMMA. Similar results were reported with the use of rifampin-filled cyclodextrin (CD) microparticles.…”