Controlled release of rhBMP-2 loaded poly(dl-lactic-co-glycolic acid)/calcium phosphate cement composites in vivo.
The release kinetics of recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded poly(dl-lactic-co-glycolic acid)/calcium phosphate cement (PLGA/Ca-P cement) composites were studied in vivo. RhBMP-2 was radiolabeled with (131)I and entrapped within PLGA microparticles or adsorbed onto the microparticle surface. PLGA microparticles were prepared of high molecular weight (HMW) PLGA (weight average molecular weight [M(w)] 49,100+/-1700) or low molecular weight (LMW) PLGA (M(w) 5,900+/-300) and used for preparation of 30:70 wt.% PLGA/Ca-P cement composite discs. Release of 131I-rhBMP-2 loaded composites was assessed by scintigraphic imaging according to a 2(2) two-level full factorial design in the rat ectopic model during four weeks. In vivo release kinetics varied among formulations. All formulations showed slow release without initial burst, and displayed a linear release from 3 to 28 days. Release of LMW entrapped rhBMP-2 composites (1.7+/-0.3%/day) was significantly faster than release from other formulations (p<0.01). After 28 days, retention within the composites was 65+/-5%, 75+/-4%, 50+/-4% and 70+/-6% of the initial rhBMP-2 for HMW entrapped, HMW adsorbed, LMW entrapped and LMW adsorbed rhBMP-2 composites, respectively. Release from the composite was probably slowed down by an interaction of rhBMP-2 and Ca-P cement after rhBMP-2 release from PLGA microparticles. We conclude that PLGA/Ca-P cement composites can be considered as sustained slow release vehicles and that the release and retention of rhBMP-2 can be modified according to the desired profile to a limited extent.
Department of Biomaterials, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
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Ruhé
O C
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Boerman
F G M
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Russel
P H M
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Spauwen
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Mikos
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Jansen
D000327:Adsorption; D000818:Animals; D001672:Biocompatible Materials; D001843:Bone Cements; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002130:Calcium Phosphates / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006016:Glycolates / Q000737:chemistry*; D019344:Lactic Acid; D008297:Male; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
D001672:Biocompatible Materials; D001843:Bone Cements; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006016:Glycolates; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C020243:calcium phosphate