Concepts for increasing gentamicin release from handmade bone cement beads

Abstract

Background and purpose: Commercial gentamicin-loaded bone cement beads (Septopal) constitute an effective delivery system for local antibiotic therapy. These beads are not available in all parts of the world, and are too expensive for frequent use in others. Thus, orthopedic surgeons worldwide make antibiotic-loaded beads themselves. However, these beads are usually not as effective as the commercial beads because of inadequate release kinetics. Our purpose was to develop a simple, cheap, and effective formulation to prepare gentamicin-loaded beads with release properties and antibacterial efficacy similar to the commercially ones.

Methods: Acrylic beads were prepared with variable monomer content: 100% (500 microL/g polymer), 75%, and 50% to increase gentamicin release through creation of a less dense polymer matrix. Using the optimal monomer content, different gel-forming polymeric fillers were added to enhance the permeation of fluids into the beads. Polyvinylpyrrolidone (PVP) 17 was selected as a suitable filler; its concentration was varied and the antibiotic release and antibacterial efficacy of these beads were compared with the corresponding properties of the commercial ones.

Results: Gentamicin release rate and the extent of release from beads prepared with 50% monomer increased when the PVP17 content was increased. Beads with 15 w/w% PVP17 released 87% of their antibiotic content. This is substantially more than the gentamicin release from Septopal beads (59%). Acrylic beads with 15 w/w% PVP17 reduced bacterial growth by up to 93%, which is similar to the antibacterial properties of the commercial ones.

Interpretation: A simple, cheap, and effective formulation and preparation process has been described for hand-made gentamicin-releasing acrylic beads, with better release kinetics and with antibacterial efficacy similar to that of the commercial ones.

Figure 1.

Cumulative percentage of gentamicin release from PMMA beads made with 100%, 75%, or 50% monomer, as a function of time during exposure to phosphate-buffered saline (PBS).

Figure 2.

Cumulative percentage of gentamicin release from PMMA beads made without filler and with 10 w/w% of PVP 17, PVP 90K, or HPMC and 50% of the prescribed amount of monomer, as a function of time during exposure to PBS.

Figure 3.

Cumulative percentage of gentamicin release from PMMA beads made with 5 w/w%, 10 w/w%, or 15 w/w% PVP 17 and 50% of the prescribed amount of monomer, as a function of time during exposure to PBS, in comparison to the gentamicin release from commercial Septopal beads. Error bars denote the SD for 3 different beads of hand-rolled and Septopal type.

Figure 4.

SEM micrographs of gentamicin-loaded, fractured acrylic beads: (A) prepared with the prescribed amount of monomer; (B) prepared with 50% of the prescribed amount of monomer. The images were taken from the fracture side of the beads. Scale bars represent 100 μm for low- and high-magnification micrographs and for the insert.

Figure 5.

Biofilm inhibition (%) as a function of time, by different gentamicin-releasing beads, calculated as a percentage UV absorbance with respect to a control, i.e. the absorbance of a biofilm grown in broth without antibiotics released from beads. Bars represent the mean ± SD of triplicate results with separately grown bacteria.