Improved bone delivery of osteoprotegerin by bisphosphonate conjugation in a rat model of osteoarthritis

  • Doschak M
  • Kucharski C
  • Wright J
 et al. 
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This study investigated the delivery of a model therapeutic protein, namely, osteoprotegerin (OPG), to bone sites in an animal model of osteoarthritis. The OPG was chemically conjugated to a "bone seeking" thiol-bisphosphonate (thiolBP) via a disulfide linkage. The BP conjugates of OPG were shown to display a higher hydroxyapatite affinity in vitro as compared to unmodified OPG. After intravenous injection, the bone uptake of OPG-thiolBP conjugate was increased 2-fold over that of control OPG under conditions of normal bone turnover. Furthermore, the retention of the OPG-thiolBP conjugate was significantly higher after 72 h. When administered to osteoarthritic rats undergoing active bone remodeling, the delivery of OPG-thiolBP conjugate to bone was increased more than 4-fold over that of control OPG after 24 h. These results suggest a significant advantage of BP conjugation as a drug delivery strategy for therapeutic cytokines in osteopenic bone diseases.

Author-supplied keywords

  • Anterior cruciate ligament
  • Bisphosphonate
  • Bone remodeling
  • Bone targeting
  • Osteoarthritis
  • Osteoprotegerin

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  • Michael R. Doschak

  • Cezary M. Kucharski

  • Jennifer E I Wright

  • Ronald F. Zernicke

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