Drug release through fibrinolysis of antibiotic-bound fibrin

  • Sato H
  • Ono K
  • Oka M
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Abstract

For the study of the sustained release of antibiotics from fibrin adhesives the antibiotic dibekacin sulfate (DKB) was covalently bound to fibrinogen with glutaraldehyde. Cross-linking reaction, treated with glutaraldehyde, however, reduced slightly the polymerizability of fibrinogen at low concentrations of glutaraldehyde. A rapid loss of polymerizability of fibrinogen was observed at concentrations above 0.05-0.1 % glutaraldehyde. Therefore, DKB was treated with approximately the lowest concentration of glutaraldehyde where fibrinogen led to have almost no polymerizability by the glutaraldehyde treatment. In vitro after the release of a large amount of DKB on the first day, there was a gradual release from DKB-bound fibrin for more than 2 weeks. Accumulated amounts of DKB for the long-term release were higher with increasing concentrations of glutaraldehyde in the cross-linking reaction. DKB-bound fibrin was also implanted in the proximal methaphysis of rat tibia. The release of DKB was detected for 2 weeks in the vicinity of bones in which the DKB-bound fibrin was implanted. The released amount of DKB, however, was very low, and regarded as one tenth of the minimum inhibitory concentration. From microscopic observation at the 14th day post-implantation, no inflammatory reaction was detected in the region of implanted portions. DKB-bound fibrin was fragmented. In gaps between these fragments newly-formed bone was observed. Thus, it appears DKB-bound fibrin is biocompatible. © 1994.

Author-supplied keywords

  • Cross-linking
  • Dibekacin sulfate (DKB)
  • Fibrinogen
  • Fibrinolysis
  • Polymerizability

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Authors

  • Hiroko Sato

  • Kozo Ono

  • Masanori Oka

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