Preparation of gentamicin dioctyl sulfosuccinate loaded poly(trimethylene carbonate) matrices intended for the treatment of orthopaedic infections

Issue title: Special issue: Advanced Functional Polymers in Medicine (AFPM): Liège, Belgium, May 2014; Guest-Editors: Christine Jérôme and Andreas Lendlein

Article type: Research Article

Authors: ter Boo, G.A.^{a; b} | Grijpma, D.W.^{b; c} | Richards, R.G.^a | Moriarty, T.F.^a | Eglin, D.^{a; *}

Affiliations: [a] AO Research Institute Davos, Davos-Platz, Switzerland | [b] Department of Biomaterials Science & Technology, University of Twente, Enschede, The Netherlands | [c] University of Groningen, University Medical Center Groningen, W.J. Kolff Institute, Department of Biomedical Engineering, Groningen, The Netherlands

Correspondence: [*] Corresponding author: D. Eglin, Musculoskeletal Regeneration program, AO Research Institute Davos, Davos, Switzerland. Tel.: +41 81 414 24 80; Fax: +41 81 414 22 88; [email protected]

Abstract: BACKGROUND: Infection is a common problem in trauma and orthopaedic surgery. Antibiotic-loaded biomaterials are used locally to clear infections as an adjunct to systemic antibiotics. Gentamicin-sulphate (GEN-SULPH) is commonly used in antibiotic-loaded biomaterials, although it displays high water solubility resulting in quick diffusion from the carrier. OBJECTIVE: Preparation of a lipophilic derivative of gentamicin to reduce solubility and obtain a slower release. Subsequently, entrapment of this lipophilic gentamicin within poly(trimethylene carbonate) (PTMC) matrices. METHODS: Hydrophobic ion-pairing was used to prepare lipophilic gentamicin (GEN-AOT). The susceptibility of Staphylococcus aureus NCTC 12973 and Staphylococcus epidermidis 103.1 for GEN-AOT was tested and the viability of fibroblasts upon exposure to GEN-AOT was assessed. GEN-AOT was then loaded into PTMC films. RESULTS: GEN-AOT was successfully prepared as confirmed by FTIR-spectroscopy. GEN-AOT was bactericidal for S. epidermidis and S. aureus at 0.5 μM and 8.5 μM, respectively. At 1.1 μM GEN-AOT no reduction in fibroblast viability was observed. At 11 μM the reduction was ∼50% . PTMC discs loaded with GEN-AOT were prepared by compression molding. CONCLUSIONS: Lipophilic GEN-AOT was at least as potent as GEN-SULPH. For S. epidermidis it was even more potent than GEN-SULPH. More than 50% fibroblast cell viability was maintained at bactericidal concentration for both bacterial strains.

Keywords: Orthopaedic infection, local infection treatment, gentamicin, antibiotic modification, poly(trimethylene carbonate), drug delivery

DOI: 10.3233/CH-151935

Journal: Clinical Hemorheology and Microcirculation, vol. 60, no. 1, pp. 89-98, 2015