Antimicrobial efficacy of a new antibiotic-loaded poly(hydroxybutyric-co-hydroxyvaleric acid) controlled release system

Objective: Failure of orthopaedic devices, mainly femoral hip replacements, due to infection is of increasing medical importance. There is a need for improved antibiotic delivery systems in the treatment of orthopaedic infections and here we have evaluated polyhydroxyalkanoate formulations for their suitability as a constant delivery system for gentamicin. Methods: Gentamicin was incorporated in poly(hydroxybutyric-co-hydroxyvalerate) (PHBV) with 8% or 12% hydroxyvalerate (HV) content at 2:1 or 5:1 (weight to weight) ratio. In conjunction with an elution study, a scanning electron microscopy and a porosity study were carried out to explore physical characteristics of the complexes before and after the leaching effect. The antibacterial effectiveness of the complexes was analysed in a bacterial adhesion assay using clinical isolates of Staphylococcus haemolyticus and Staphylococcus aureus. In addition, the polymers were exposed to pooled human blood to test their biocompatibility in both static and dynamic environments. Results: We have shown that increasing the HV content from 8% to 12% leads to a faster release of the integrated antibiotic. An increase in antibiotic content enhanced the homogeneity while decreasing the permeability of the complexes and reducing the release rate. A significant reduction in the number of the adherent S. aureus and gentamicin-resistant S. haemolyticus within a 48h exposure to our formulations confirmed the effectiveness of the PHBV/gentamicin complexes. Finally, these formulations did not alter the haemodynamics of the pooled blood samples after an extended period of time. Conclusion: Taken together, the PHBV/gentamicin formulations may prove to be effective preventive therapeutic modalities in implant-related Staphylococcus infections.