In vitro and in vivo testing of bioabsorbable antibiotic containing bone filler for osteomyelitis treatment
In vitro and in vivo testing of bioabsorbable antibiotic containing bone filler for osteomyelitis treatment
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DOI：
10.1002/jbm.a.30766
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发表时间：
2006-09-01
影响因子：
4.9
通讯作者：
Aro, Hannu T.
中科院分区：
文献类型：
--
作者：
Koort, Jyri K.;Suokas, Esa;Aro, Hannu T.
使用局部抗生素的生物可降解植入物是治疗慢性骨髓炎的一个有吸引力的概念。我们的目的是开发一种新的药物释放系统的基础上控制环丙沙星从聚（N/L-乳酸）。由生物可吸收的聚（D/L-丙交酯）基质和环丙沙星（7.4重量%）制造圆柱形复合颗粒（1.0 × 0.9 mm）。进行了体外研究，以描绘抗生素的释放曲线，并通过MIC测试验证其抗微生物活性。在兔中进行长期研究以验证环丙沙星从体内复合物中的释放。环丙沙星的治疗水平（> 2 μ g/mL）保持在60至300天之间，并且浓度保持低于体外20 μ g/mL的潜在有害水平。释放的环丙沙星保留了其对常见病原体的抗菌性能。在一项对3只家兔进行的探索性长期体内研究中，胫骨中度充盈（160 mg）后（随访168天），无法从血清中检测到环丙沙星，而在高剂量（双侧胫骨总剂量为1000 mg）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 ng/mL）。在168和300天时，可在所有样品中测量环丙沙星的骨浓度。测试的共聚丙交酯基质似乎是一个有前途的选择，在选择可吸收的载体持续释放的抗生素，但复合材料需要修改，以促进环丙沙星释放在植入的前60天。(c)2006 Wiley Periodicals，Inc.
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(n/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 mu g/mL) was maintained between 60 and 300 days and the concentration remained below the potentially detrimental level of 20 mu g/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, cip-rofloxacin 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 1000 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. (c) 2006 Wiley Periodicals, Inc.