Cefuroxime-impregnated calcium phosphates as an implantable delivery system in experimental osteomyelitis

Abstract

The study aimed to investigate the effectiveness of porous calcium phosphates viz., hydroxyapatite (HAp) and a bi-phasic calcium phosphate (BCP) with predominately β-tricalcium phosphate (β-TCP) prepared by aqueous solution combustion method impregnated with cefuroxime axetil for the treatment of experimental osteomyelitis and compared with parenteral treatment. In vitro release of the drug was tested for its sustained elution characteristics for 21 days in PBS (pH 7.2) and measured by HPLC. In the in vivo study, bone infection was induced in tibia of rabbits by inoculation of 1 ml (3 × 10 6) CFU Staphylococcus aureus. On the 21st day, after the development of osteomyelitis, six animals were treated by filling the cavity with cefuroxime-impregnated HAp blocks (Group II), six animals with the same drug-impregnated β-TCP (Group III) and in six others, only cefuroxime (15 mg/kg twice daily) was injected parenterally 6 weeks (Group IV). Group I with six animals was kept untreated. Histologically, the signs of infection were found to subside by 3 and 6 weeks. Radiological evaluation with cefuroxime-impregnated HAp and β-TCP pointed out the disappearance of sequestrum and existence of newly formed bony specules. Concentration of cefuroxime in bone and serum as estimated by HPLC showed highest value on day 21 itself which reduced marginally by day 42 in both the groups and these values were higher than minimum inhibitory concentration (MIC) against S. aureus. Our findings suggest that bi-phasic calcium phosphates with predominately β-TCP content is a very efficient carrier material for antibiotic compounds even for refractory infections by S. aureus.