Benoit M A, Mousset B, Delloye C, Bouillet R, Gillard J
Louvain Catholic University, Brussels, Belgium.
Int Orthop. 1997;21(6):403-8. doi: 10.1007/s002640050195.
Plaster of Paris implants containing vancomycin (60 mg/g of carrier) were prepared in order to be used as local delivery system for the treatment of bone infections. The regulation of the release rate was performed by coating the carrier with a polylactide-co-glycolide polymer composed by 10% (w/w) polyglycolic acid and 90% (w/w) racemic poly (D,L-lactic acid). The release of the antibiotic from the biodegradable matrix was evaluated in vitro. From this investigation, it is clear that the drug elution depends on the coating depth. After a burst effect occurring on the first day of the experiment, therapeutic concentrations were measured during one week when uncoated implants were used. The coating allowed decrease of the burst effect and extended efficient release to more than five weeks when the implants were embedded with six layers (162 microns) of PLA45GA10. This delivery system was implanted into the femoral condyle of rabbits. It was shown that the in vivo release was also closely regulated by the coating depth. In all bone tissues (bone marrow and cortical bone) surrounding the pellets, the drug concentration exceeded the Minimum Inhibitory Concentration for the common causative organisms of bone infections (Staphylococcus aureus) for at least four weeks without inducing serum toxic levels. Due to its cheapness, facility of use and sterilization, biocompatibility and biodegradability, plaster of Paris coated with PLA45GA10 polymer giving a controlled release of vancomycin appears to be a promising sustained release delivery system of antibiotics for the treatment of bone and joint infections.
制备了含万古霉素(60毫克/克载体)的巴黎石膏植入物,用作治疗骨感染的局部给药系统。通过用由10%(重量/重量)聚乙醇酸和90%(重量/重量)外消旋聚(D,L-乳酸)组成的聚丙交酯-乙交酯聚合物包被载体来调节释放速率。在体外评估了抗生素从可生物降解基质中的释放情况。从这项研究可以清楚地看出,药物洗脱取决于包被深度。在实验的第一天出现突释效应后,使用未包被的植入物时,在一周内测量到了治疗浓度。当植入物包被六层(162微米)PLA45GA10时,包被可减少突释效应,并将有效释放延长至五周以上。将该给药系统植入兔股骨髁。结果表明,体内释放也受到包被深度的密切调节。在丸剂周围的所有骨组织(骨髓和皮质骨)中,药物浓度超过了骨感染常见病原体(金黄色葡萄球菌)的最低抑菌浓度,至少持续四周,且未引起血清毒性水平。由于其价格低廉、使用和灭菌方便、生物相容性和生物可降解性,包被有PLA45GA10聚合物并能控释万古霉素的巴黎石膏似乎是一种有前景的用于治疗骨和关节感染的抗生素缓释给药系统。