Koort Jyri K, Suokas Esa, Veiranto Minna, Mäkinen Tatu J, Jalava Jari, Törmälä Pertti, Aro Hannu T
Department of Orthopaedic Surgery and Traumatology, Orthopaedic Research Unit, University of Turku, Turku, Finland.
J Biomed Mater Res A. 2006 Sep 1;78(3):532-40. doi: 10.1002/jbm.a.30766.
The use of local antibiotics from a biodegradable implant is appealing concept for treatment of chronic osteomyelitis. Our aim was to develop a new drug delivery system based on controlled ciprofloxacin release from poly(D/L-lactide). Cylindrical composite pellets (1.0 x 0.9 mm) were manufactured from bioabsorbable poly(D/L-lactide) matrix and ciprofloxacin (7.4 wt %). In vitro studies were carried out to delineate the release profile of the antibiotic and to verify its antimicrobial activity by means of MIC testing. A long-term study in rabbits was performed to validate the release of ciprofloxacin from the composite in vivo. Therapeutic level of ciprofloxacin (>2 microg/mL) was maintained between 60 and 300 days and the concentration remained below the potentially detrimental level of 20 microg/mL in vitro. The released ciprofloxacin had retained its antimicrobial properties against common pathogens. In an exploratory long-term in vivo study with three rabbits, ciprofloxacin could not be detected from the serum after moderate filling (160 mg) of the tibia (follow-up 168 days), whereas after high dosing (a total dose of 1,000 mg in both tibias) ciprofloxacin was found temporarily at low serum concentrations (14-34 ng/mL) during the follow-up of 300 days. The bone concentrations of ciprofloxacin could be measured in all samples at 168 and 300 days. The tested copolylactide matrix seems to be a promising option in selection of resorbable carriers for sustained release of antibiotics, but the composite needs modifications to promote ciprofloxacin release during the first 60 days of implantation.
利用可生物降解植入物局部应用抗生素是治疗慢性骨髓炎的一个有吸引力的概念。我们的目标是开发一种基于聚（D/L-丙交酯）控制释放环丙沙星的新型药物递送系统。由生物可吸收的聚（D/L-丙交酯）基质和环丙沙星（7.4 wt%）制成圆柱形复合微丸（1.0×0.9毫米）。进行体外研究以描绘抗生素的释放曲线，并通过MIC测试验证其抗菌活性。在兔子身上进行了一项长期研究，以验证环丙沙星在体内从复合物中的释放情况。环丙沙星的治疗水平（>2微克/毫升）在60至300天之间维持，且浓度在体外保持低于潜在有害水平的20微克/毫升。释放的环丙沙星对常见病原体保留了其抗菌特性。在对三只兔子进行的探索性长期体内研究中，胫骨适度填充（160毫克）后168天的随访期间，血清中未检测到环丙沙星，而在高剂量给药（双侧胫骨总剂量1000毫克）后，在300天的随访期间发现环丙沙星暂时处于低血清浓度（14 - 34纳克/毫升）。在168天和300天的所有样本中都可以测量环丙沙星的骨浓度。所测试的共聚丙交酯基质似乎是选择用于抗生素持续释放的可吸收载体的一个有前景的选择，但该复合物需要改进以促进植入后前60天内环丙沙星的释放。
