Preparation and evaluation of biodegradable microspheres containing a new potent osteogenic compound and new synthetic polymers for sustained release.
In order to achieve the sustained release of 3-ethyl-4-(4-methylisoxazol-5-yl)-5-(methylthio) thiophene-2-carboxamide (BFB0261), a new potent osteogenic compound for the treatment of bone disorders, we prepared microspheres containing BFB0261 and newly synthesized three poly (D, L-lactic acid) (PLA), four poly (D, L-lactic acid-co-glycolic acid) (PLGA), and eight poly (D, L-lactic acid)-block-poly(ethylene glycol) (PLA-PEG) biodegradable polymers or copolymers, and evaluated the release pattern of BFB0261 from the microspheres in vitro and in vivo. The mean particle size of the microspheres, except for the microspheres constructed from PLA-PEG with a greater than 20% PEG component, was in the range of approximately 10-50 microm, and the preparations showed a spherical shape with a smooth surface. In an in vitro release study, the release of BFB0261 from PLA-1 (Mw: 36 kDa), PLAPEG9604H (PLA/PEG ratio: 96:4, Mw: 181 kDa), or PLAPEG8317 (PLA/PEG ratio: 83:17, Mw: 106 kDa) microspheres occurred in a zero-order manner with a slow release, and more than 50% of BFB0261 remained in each type of microsphere at 12 weeks after incubation. When the BFB0261 microspheres constructed from various polymers were intramuscularly administered to the rat femur, the microspheres constructed from PLA-1 or PLAPEG9604H were able to achieve a sustained release of BFB0261 at the injection site for 6 weeks. The present information indicates that microspheres constructed from PLA-1 or PLAPEG9604H may be feasible for bone engineering.
Department of Pharmaceutical Engineering, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
Nobuo
N
Umeki
Takayuki
T
Sato
Masahiro
M
Harada
Junko
J
Takeda
Shuji
S
Saito
Yasunori
Y
Iwao
Shigeru
S
Itai
D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004339:Drug Compounding; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D005360:Fibula / Q000187:drug effects / Q000378:metabolism; D007555:Isoxazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010012:Osteogenesis / Q000187:drug effects*; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D013876:Thiophenes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
C551895:3-ethyl-4-(4-methylisoxazol-5-yl)-5-(methylthio)thiophene-2-carboxamide; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007555:Isoxazoles; D011108:Polymers; D013876:Thiophenes