Controlled release of bisphosphonate from a calcium phosphate biomaterial inhibits osteoclastic resorption in vitro.
Calcium phosphate biomaterials such as calcium deficient apatite (CDA) have been contemplated as carrier for delivery of bisphosphonate in bone tissues. In the present work, we have investigated the in vitro biological properties of Zoledronate-loaded CDA. CDA was loaded with zoledronate according to a previously described coating process. 31P MAS NMR spectra demonstrated the effective loading of zoledronate onto CDA. Using 14C labeled zoledronate, we then demonstrated the in vitro release of zoledronate from CDA. In a first set of experiments, we confirmed that Zoledronate reduced the number of TRAP-, vitronectin receptor-, and F-actin ring-positive cells as well as the resorption activity of osteoclasts obtained from a total rabbit bone cell culture. Interestingly, Zoledronate-loaded CDA and its extractive solutions decreased the osteoclastic resorption. Finally, zoledronate-loaded CDA did not affect the viability and alkaline phosphatase activity of primary osteoblastic cells. These data demonstrate that CDA is effective for loading and release of zoledronate. The released zoledronate inhibited osteoclastic resorption without affecting osteoblasts. Our findings therefore suggest that such a drug delivery system would allow an increase in the efficiency of bisphosphonates by being locally available. Further experiments are now required to evaluate the in vivo antiresorptive activity of this concept.
Faucheux
C
C
INSERM, U791, LIOAD, Nantes, F-44042 France.
Verron
E
E
Soueidan
A
A
Josse
S
S
Arshad
M D
MD
Janvier
P
P
Pilet
P
P
Bouler
J M
JM
Bujoli
B
B
Guicheux
J
J
D000818:Animals; D001031:Apatites / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D050071:Bone Density Conservation Agents / Q000378:metabolism*; D001862:Bone Resorption / Q000378:metabolism*; D002130:Calcium Phosphates / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D004164:Diphosphonates / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D007093:Imidazoles / Q000378:metabolism*; D008422:Materials Testing; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D000077211:Zoledronic Acid
D001031:Apatites; D001672:Biocompatible Materials; D050071:Bone Density Conservation Agents; D002130:Calcium Phosphates; D004164:Diphosphonates; D004337:Drug Carriers; D007093:Imidazoles; D000077211:Zoledronic Acid; C020243:calcium phosphate