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

G A ter Boo, D W Grijpma, R G Richards, T F Moriarty, D Eglin

Index: Clin. Hemorheol. Microcirc. 60 , 89-98, (2015)

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Abstract

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.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.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.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.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.