Growth hormone-loaded macroporous calcium phosphate ceramic: in vitro biopharmaceutical characterization and preliminary in vivo study.
Calcium phosphate ceramics recently have been used for administering therapeutic agents in bone. The present work investigated the efficacy of macroporous biphasic calcium phosphate (MBCP) implants as a matrix for local delivery of human growth hormone (hGH). An initial study showed that the release of 5 microg of hGH loaded onto MBCP cylinders was rapid during the first 48 h and sustained for a total of 11 days. The biological integrity of hGH (88.2%) was checked using a specific bioassay (cellular proliferation of hGH-sensitive Nb2 cells) in comparison with a radioimmunoassay to calculate the proportion of bioactive hGH released. MBCP cylinders then were loaded with 1, 10, and 100 microg of hGH and implanted into rabbit femurs (n = 16) to determine hGH effects on bone ingrowth and ceramic resorption, as evaluated by scanning electron microscopy and image analysis. Results indicated that hGH increased bone ingrowth and ceramic resorption significantly in comparison with contralateral and control implants. Biochemical parameters monitored in rabbit plasma showed that hGH did not produce detectable systemic effects. Thus the use of MBCP appears to be effective for local delivery of hGH and for increasing bone ingrowth.
Guicheux
J
J
Laboratoire de recherche sur les matériaux d'intérêt biologique, UPRES 2159, Faculté de Chirurgie Dentaire, Nantes, France.
Gauthier
O
O
Aguado
E
E
Heymann
D
D
Pilet
P
P
Couillaud
S
S
Faivre
A
A
Daculsi
G
G
D000042:Absorption; D000818:Animals; D001702:Biopharmaceutics; D018786:Bone Substitutes; D002130:Calcium Phosphates / Q000493:pharmacokinetics*; D002516:Ceramics / Q000493:pharmacokinetics*; D004337:Drug Carriers; D005260:Female; D019382:Human Growth Hormone / Q000493:pharmacokinetics*; D008422:Materials Testing; D011817:Rabbits; D051381:Rats
D018786:Bone Substitutes; D002130:Calcium Phosphates; D004337:Drug Carriers; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D019382:Human Growth Hormone; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous