Profile of rhBMP-2 release from collagen minipellet and induction of ectopic bone formation.
For a cylindrical controlled-release formulation using collagen as a carrier, called the minipellet (MP), which contains rhBMP-2, the relationship between the diameter of MPs and rhBMP-2 release profiles was investigated, and its effect in inducing bone formation was evaluated. Samples with three different diameters were tested for each of the following formulations: MP without additives, MP with 10% (w/w) glutamic acid (Glu) and 20% (w/w) alanine (Ala), and MP with 20% (w/w) Glu and 20% (w/w) Ala. The results of the in vitro release test and the amount of rhBMP-2 remaining in the MPs after subcutaneous implantation into mice were compared among different samples. It was found that the addition of Glu accelerated release of rhBMP-2 effectively. Release was accelerated as the diameter of MP became smaller and the amount of Glu added increased. The amount of calcium formed in 3 weeks after subcutaneous implantation into mice was dose-dependent. The amount of calcium formed per unit rhBMP-2 dose tended to increase as the diameter of MP became smaller and the amount of Glu added became greater; calcification was thus associated with release rate. These results indicate that MPs with smaller diameters induce bone formation more efficiently. For use in the treatment of fracture, etc., MP is considered to be a suitable dosage form, which can be administered noninvasively.
Maeda
Hiroo
H
Formulation Research Laboratories, Sumitomo Pharmaceuticals Co. Ltd., Osaka, Japan. maedah@sumitomopharm.co.jp
Sano
Akihiko
A
Fujioka
Keiji
K
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003094:Collagen; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010012:Osteogenesis / Q000187:drug effects*; D016212:Transforming Growth Factor beta
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D016212:Transforming Growth Factor beta; D003094:Collagen