Peer-reviewed veterinary case report
Improved bone delivery of osteoprotegerin by bisphosphonate conjugation in a rat model of osteoarthritis.
- Journal:
- Molecular pharmaceutics
- Year:
- 2009
- Authors:
- Doschak, Michael R et al.
- Affiliation:
- Faculty of Pharmacy & Pharmaceutical Sciences and Department of Chemical & Materials Engineering · Canada
- Species:
- rodent
Abstract
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.
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Search related cases →Original publication: https://pubmed.ncbi.nlm.nih.gov/19718808/