Biodegradable implantable fluconazole delivery rods designed for the treatment of fungal osteomyelitis: influence of gamma sterilization.
Fluconazole poly(D,L-lactic) acid (PLA) and poly(L-lactic) acid (L-PLA) implantable delivery rods were studied, in vitro and in vivo, as an alternative treatment of fungal osteomyelitis. Implantable rods loaded with 5% fluconazole (FLU) were prepared by the injection-molding method and sterilized by gamma-irradiation at a dose of 25 kGy. Loading efficiency, physical chemistry (high performance liquid chromatography, X-ray diffraction, gel permeation chromatography), and in vitro and in vivo release assays were performed to evaluate the novel delivery systems and the sterilization effect on implant characteristics. In spite of polymer degradation after gamma-irradiation, the loading efficiency, chemical stability, and crystallographic structure of FLU were not affected. In vivo studies were carried out in femoral bone marrow of rabbits. Approximately 85 and 80% of the total dose were released within 12 and 4 weeks from PLA and L-PLA rods, respectively. This showed a faster release rate of FLU in vivo than in vitro, showing almost zero-order kinetics from PLA rods.
Soriano
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I
Departamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, Tenerife, Spain. msoriano@ull.es
Martín
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AY
Evora
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C
Sánchez
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E
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials; D016503:Drug Delivery Systems; D015725:Fluconazole / Q000008:administration & dosage*; D005720:Gamma Rays; D019344:Lactic Acid; D008297:Male; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology; D011091:Polyesters; D011108:Polymers; D011817:Rabbits; D013242:Sterilization
D000935:Antifungal Agents; D001672:Biocompatible Materials; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D015725:Fluconazole