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. © 2009 American Chemical Society.
CITATION STYLE
Doschak, M. R., Kucharski, C. M., Wright, J. E. I., Zernicke, R. F., & Uludag, H. (2009). Improved bone delivery of osteoprotegerin by bisphosphonate conjugation in a rat model of osteoarthritis. Molecular Pharmaceutics, 6(2), 634–640. https://doi.org/10.1021/mp8002368
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