Effects of bead size and polymerization in PMMA bone cement on vancomycin release

Abstract

Polymethylmethacrylate (PMMA) bone cement loaded with antimicrobial agents is used for the treatment and prevention of infections in orthopaedic surgery. The use of antimicrobial-loaded bone cement allows for high local doses while avoiding systemic toxicity. The release of vancomycin (VCM) from bone cement has been reported. However, the exact mechanism behind the release is unknown. We studied the influence of bead size and polymerization time on elution, and considered the release mechanism for VCM. We used CMW Endurance Bone Cement^®. Cements were prepared by mixing 6 g of VCM with 40 g of polymer, and then 10 g of liquid monomer was added. We kneaded and shaped the preparation into spheres containing 10.7 w/w% VCM. We measured the release of VCM from PMMA beads of three different sizes. Average weights of the beads were 0.96 g (SB) (n=6), 2.86 g (MB) (n=2) and 5.65 g (LB) (n=1). Additionally, we studied beads made with different polymerization times. The polymerization time was taken as the period from the making of the beads until the start of the study, and was 15 min (B15), 20 min (B20), 60 min (B60) or 180 min (B180). The release of VCM showed a bimodal curve with a high initial release followed by a sustained release. Regarding the size of the beads, SB released 7.2%, MB released 4.3% and LB released 3.1%. Regarding polymerization time, B15 released 10.0%, B20 released 6.5%, B60 released 6.3% and B180 released 4.3%, respectively. The release of VCM from PMMA beads was influenced by bead size and polymerization time. Those beads which were smaller and had a shorter polymerization time released more VCM. Total pore volume of beads that polymerization time was 30 min after drug-release test was 1.33 times grater than that of control beads that polymerization time was one week before drug-release test. This suggested that the short polymerization time caused the beads to leak more VCM. We proposed a model with four kinds of the dissolution from bone cement. (A) Dissolution from drug particles on the cement surface. This type shows the burst effect of release curve. (B) Dissolution from micropores near the cement surface. It is responsible the grater part of the curve based on Higuchi's equation. (C) Dissolution from ink-bottle-neck-type micropores. It causes a release based on a non-Higuchi's equation. (D) No dissolution from Encapsulation micropores.

It can be concluded that the release of VCM from bone cements is controlled by a combination of surface area and polymerization time. PMMA beads loaded with VCM should be used carefully in orthopaedic surgery, taking into consideration the influence of bead size and polymerization time.