Study of the release kinetics of dalbavancin from bone allografts

Bone infections are common and difficult to treat, and secondary bone defects, which are often observed, may require a bone allograft. In this case, the surgeon will add antibiotics (usually vancomycin) in direct contact with the bone graft during the procedure, in order to allow in-situ release after implantation in the operating site. Dalbavancin is a novel antibiotic indicated for treating acute bacterial infections resistant to vancomycin. Its modified chemical structure grants it an increased half-life that could modify its release kinetics from the bone allograft. The aim of this study was to determine the release kinetics of dalbavancin from bone grafts after they were immersed in a dalbavancin solution. The study was conducted using a Design of Experiments (DoE) protocol. Decellularized and delipidated allograft bone cubes were preliminarily characterized and put into contact with dalbavancin solutions. The parameters that were studied where the allograft mass, initial dalbavancin concentration and contact time. The samples were then transferred into the release media, which was sampled over time and dalbavancin was quantified using a high pressure liquid chromatography with diode array detector method that was developed for the occasion. Our results showed that on average, dalbavancin was fully released after 5 min for the lower mass bone grafts, but after 60 min for the high mass and high concentration conditions. Contact time had no impact, thus indicating a fast loading process of dalbavancin into the allograft. Although our study revealed the possible benefits of using dalbavancin in bone grafting, an in-vivo study is required to confirm our hypotheses.

Graphical Abstract