RESUMO
Introduction: Breast cancer is one of the most frequent primary tumors that cause spinal metastases. Metastasis consequences impair both the patient's overall prognosis and quality of life. We previously developed a porous hydroxyapatite collagen composite (HAp/Col) as an osteoconductive scaffold. HAp/Col is a commercially available artificial bone that is frequently utilized in spinal fusion. Because of its high absorbance capacity, HAp/Col is regarded as a good chemical carrier. Methods: This study investigated the effect of local administration of paclitaxel combined with HAp/Col scaffold on breast cancer metastasis. High-performance liquid chromatography was used to assess the in vitro release of paclitaxel from HAp/Col. In an in vivo rat model, the inhibitory effects of paclitaxel-impregnated scaffolds on local osteogenesis was examined, and then the local suppression effects on metastatic cancer were investigated. Results: In vitro testing revealed that roughly 30% of the paclitaxel was released within 96 hours. Paclitaxel-impregnated HAp/Col inhibited local osteogenesis for the first 8 weeks in a rat femur. However, at 12 weeks following surgery, this negative effect appeared to have subsided. In the metastatic model, all rats in the control group reached the humane endpoint 14 days after surgery. On the other hand, the average time to the endpoint in the paclitaxel group was 26.5 days, which was substantially longer than that in the control group. Long-term survivors treated with paclitaxel had no remaining tumor cells in the femoral bone, and osteogenesis was seen surrounding the HAp/Col. Conclusions: Paclitaxel-impregnated HAp/Col reduced local tumor development and extended the time to the target endpoint in rats with metastases from breast cancer. This study shows that local implantation of paclitaxel-impregnated HAp/Col may be a viable therapeutic option for the management of breast cancer metastases.
RESUMO
Osteomyelitis remains one of the most challenging disorders for orthopedic doctors despite the advancement of therapeutic techniques. The purpose of this study was to investigate the feasibility of local antibiotic administration using hydroxyapatite/collagen (HAp/Col) as a drug delivery system. We hypothesized that higher adsorbability of antibiotics onto HAp/Col will result in more efficacious activity and therefore, treatment of osteomyelitis. Eight antibiotics were examined in this study: amikacin, cefazolin, cefotiam, daptomycin, minocycline, piperacillin, teicoplanin, and vancomycin. Aligning with their adsorbability onto HAp/Col, minocycline, teicoplanin, and vancomycin showed antibacterial effects up to 14 days after subcutaneous implantation in Wistar rats; while antibiotics with reduced adsorbability (cefazolin, cefotiam, piperacillin) had diminished antibacterial effects. Furthermore, when implanted into a rat femur, vancomycin levels from the Hap/Col were detected in the medullary space above the minimum inhibitory concentration for Staphylococcus aureus for 7 days, while cefazolin levels were undetectable. Aligning with these results, implantation of Hap/Col impregnated with vancomycin to the femur in an acute osteomyelitis rat model had a greater therapeutic effect than cefazolin, as measured by the number of bacteria, the extent of bone destruction, and bone regeneration. These results indicated that the adsorbability of antibiotics onto their carrier is important when locally administered and that HAp/Col scaffolds might be a useful antibiotic delivery system for osteomyelitis. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 38:843-851, 2020.