Preparation and evaluation of biodegradable films containing the potent osteogenic compound BFB0261 for localized delivery.
To achieve sustained release of 3-ethyl-4-(4-methylisoxazol-5-yl)-5-(methylthio) thiophene-2-carboxamide (BFB0261), a new potent osteogenic compound for treating bone disorders, we prepared film formulations containing BFB0261 and the following newly synthesized biodegradable polymers by a solvent casting technique: poly(D,L-lactic acid) (PLA), poly(D,L-lactic acid-co-glycolic acid) (PLGA), poly(D,L-lactic acid)-block-poly(ethylene glycol) (PLA-PEG), and poly(D,L-lactic acid-co-trimethylene carbonate) (PLA-TMC) polymers or copolymers. Powder X-ray diffractometry (PXRD), differential thermal analysis (DTA), scanning electron microscopy (SEM), and tensile testing were performed to examine the physicochemical properties of these films. Almost all the films exhibited a smooth and homogeneous surface, as observed by SEM. In addition, PXRD and DTA revealed that BFB0261 existed in an amorphous state in the films. The in vitro release of BFB0261 from PLA100 (M(w): 251 kDa), PLAPEG9604H (PLA/PEG ratio: 96:4; M(w): 181 kDa), PLAPEG8515H (PLA/PEG ratio: 85:15; M(w): 51.5 kDa), or PLAPEG8020 (PLA/PEG ratio: 80:20; M(w): 33.7 kDa) films followed zero-order kinetics with slow release up to 12 weeks following incubation. Although release of BFB0261 from PLA-TMC films followed first-order kinetics, sustained release of BFB0261 for 12 weeks was still observed for PLATMC8416 (PLA/TMC ratio: 84:16; M(w): 170 kDa) films. Furthermore, when the BFB0261-loaded films constructed from various polymers were implanted subcutaneously on rat backs, the PLAPEG8515H and PLATMC8416 films were capable of achieving sustained release of BFB0261 at the administrated site for 12 weeks. Therefore, the present data indicate that films constructed from PLAPEG8515H or PLATMC8416 may be applicable to bone or tissue engineering.
Department of Pharmaceutical Engineering, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Nobuo
N
Umeki
Takayuki
T
Sato
Masahiro
M
Harada
Junko
J
Takeda
Shuji
S
Saito
Yasunori
Y
Iwao
Shigeru
S
Itai
D000818:Animals; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004343:Drug Implants; D005260:Female; D007555:Isoxazoles / Q000008:administration & dosage* / Q000737:chemistry; D007700:Kinetics; D007773:Lactates / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis / Q000187:drug effects*; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D033362:Powder Diffraction; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D013718:Tensile Strength; D013876:Thiophenes / Q000008:administration & dosage* / Q000737:chemistry; D014961:X-Ray Diffraction
C551895:3-ethyl-4-(4-methylisoxazol-5-yl)-5-(methylthio)thiophene-2-carboxamide; D004337:Drug Carriers; D004343:Drug Implants; D007555:Isoxazoles; D007773:Lactates; D011091:Polyesters; D011108:Polymers; D013876:Thiophenes; C088513:poly(lactic acid-ethylene glycol); C121059:poly(lactide-co-trimethylene carbonate); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide)