Bone affinity of a bisphosphonate-conjugated protein in vivo.
Growth factors capable of stimulating bone formation are potential therapeutic agents for osteoporosis treatment. It is essential, however, that a targeting mechanism is incorporated into the growth factors to deposit them at osseous tissue with minimal distribution to extraskeletal sites. To this end, a strategy has been developed in which a bone-seeking molecule, 1-amino-1,1-diphosphonate methane (aminoBP), was chemically conjugated to a model protein, bovine serum albumin (BSA). This study was carried out to assess the bone affinity of the conjugates in a tibia injection model. Using ovariectomized (OVX) rats, initial (3 h) retention of BSA and aminoBP-BSA were found to be equivalent when injected into the medullary cavity of tibia. After 1 day, an 8- and 12-fold higher tibiae retention of the protein was obtained in normal and OVX rats as a result of aminoBP conjugation. A similar result ( approximately 12-fold difference) was also obtained in OVX rats after 3 days. We concluded that aminoBP conjugation to BSA imparted a high bone affinity and enhanced bone retention of proteins in normal and OVX rats.
Uludag
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Department of Biomedical Engineering, 1098 EDC Building, Faculty of Medicine, University of Alberta, Edmonton, Alberta T6G 2V2, Canada. hasan.uludag@ualberta.ca
Gao
T
T
Wohl
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GR
Kantoci
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D
Zernicke
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RF
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D004164:Diphosphonates / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D010024:Osteoporosis / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000378:metabolism*
D004164:Diphosphonates; D012710:Serum Albumin, Bovine