In vivo-in vitro study of biodegradable and osteointegrable gentamicin bone implants.
Three implants composed of phosphate (25% hydroxyapatite, 75% tricalcium phosphate), 20% poly(DL-lactide) (DL-PLA; weight-average molecular weight (Mw), 30 kD) and 3% gentamicin sulphate (GS) were assayed in vitro and in vivo to study their release profiles as potential drug delivery systems to prevent or treat osteomyelitis. To prolong GS release, some implants were coated with poly(lactide-co-glycolide) (PLGA; Mw, 100 kD; I-PLGA) or DL-PLA (Mw, 200 kD; I-PLA). GS levels were measured in bone, kidney and blood after implantation into the femur of rats. The release profiles show a burst in the first few days, followed by a slower release rate. After I-PLA implantation, bone antibiotic concentrations higher than the minimum bactericidal concentration were maintained for 4 weeks. A linear correlation between in vitro and in vivo GS release was found to continue until complete drug release. Histological and radiological analysis showed that the implants were well tolerated and gradual new bone formation was observed.
Sánchez
E
E
Departamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200 La Laguna, Spain.
Baro
M
M
Soriano
I
I
Perera
A
A
Evora
C
C
D020341:Absorbable Implants; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D005839:Gentamicins