Release of recombinant human bone morphogenetic protein 2 from a newly developed carrier.
After implantation of a polymer-coated gelatin sponge (PGS) containing either 0.4 or 1.0 mg of 125I-rhBMP-2 for each 1 cm(3) of PGS into the right ulnar of rabbits, changes in the level of radioactivity at the implant site and in the blood were measured for 21 days after implantation, and the cumulative excretion ratio of radioactivity in the urine and feces was calculated. For both doses, radioactivity at the implant site was eliminated biphasically. The concentration of trichloroacetic acid (TCA)-precipitable radioactivity in the blood reached a maximum 6 h after implantation, at which time it was equivalent to 1.41% of the administered dose (0.4 mg/cm(3)). The remaining radioactivity was eliminated rapidly thereafter, falling below the detection limit within 48 h. The t(1/2alpha) was about 0.1 days, the t(1/2beta) was about 3 days, and the mean resident time (MRT) value was about 4 days. By 17 days after implantation, 88.1% of the administered radioactivity had been excreted in the urine, and 1.7% had been excreted in the feces. TCA precipitation test results indicated that most of the radioactivity excreted in urine was a low-molecular weight decomposition product. At 21 days after implantation, the radioactivity of the PGS implant site had declined to 0.5% of the administered amount. Autoradiographs of the implant site taken 28 days after implantation revealed that, at both doses, the residual radioactivity was confined to the area of the implanted PGS. These results indicate that PGS retains an appropriate amount of recombinant human bone morphogenetic protein 2 (rhBMP-2) at the orthotopically implanted site for at least 21 days enough to induce bone regeneration. Thus, PGS shows great clinical potential as a carrier for rhBMP-2.
Yokota
S
S
Institute for Drug Development and Research, Yamanouchi Pharmaceutical Co, Ltd, 180 Ozumi, Yaizu-shi, Shizuoka 425-0072, Japan. yokota_s@yamanouchi.co.jp
Uchida
T
T
Kokubo
S
S
Aoyama
K
K
Fukushima
S
S
Nozaki
K
K
Takahashi
T
T
Fujimoto
R
R
Sonohara
R
R
Yoshida
M
M
Higuchi
S
S
Yokohama
S
S
Sonobe
T
T
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D011108:Polymers / Q000008:administration & dosage / Q000493:pharmacokinetics; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D011108:Polymers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta