盐酸环丙沙星聚乳酸-羟基乙酸共聚物缓释微球在Gustilo Ⅱ型开放性骨折一期内固定辅助治疗中的应用

目的 制备具有良好降解性及缓释效果的负载盐酸环丙沙星(CIP)的聚乳酸-羟基乙酸共聚物(PLGA)微球(CIP-PLGA-MS),观察其在Gustilo Ⅱ型开放性骨折一期内固定辅助治疗中的作用.方法 采用乳化溶剂挥发法制备微球,检测微球表面形态、产率、载药量、包封率、体外释药曲线等.建立SD大鼠股骨金黄色葡萄球菌(ATCC25923)感染性Gustilo Ⅱ型开放性骨折动物模型,共36只并随机分成对照组A和实验组B,每组18只.感染2h后行清创缝合克氏针髓内固定术,分别植入空白微球和载药微球于大鼠骨折断端.28d后通过X线、病原微生物学评估患肢是否感染.结果 成功制备具有良好缓释性能的CIP-PLGA-MS.微球粒径集中分布于30～100μm范围.产率、载药量、包封率分别达71.37%、4.82%、13.75%.微球24h内突释效应明显,28d累积释放率达71.8%.实验组大鼠感染治愈率为94.44%,对照组为61.11%,差异有统计学意义(P<0.05).结论 CIP-PLGA-MS能够有效辅助降低Gustilo Ⅱ型开放性骨折一期内固定治疗的感染率.

Abstract：

Objective The aim of this study was to prepare poly (D, L-lactide-co-glycolide) (PLGA) biodegradable microspheres loaded with Ciprofloxacin (CIP-PLGA-MS) and to evaluate its adjuvant efficiency for the internal fixation treatment of Gustilo Ⅱ type open fracture. Methods CIP-PLGA-MS was prepared by the double emulsion solvent evaporation method. The microsphere size, morphological characteristics, production yield, drug content, encapsulation efficiency, in vitro release had been detected. The model of Gustilo Ⅱ type open fracture infected with Staphylococcus aureus (ATCC25923) were created in 36 rats which were divided into group A (control group) and group B (experimental group). Sterilized blank microspheres and CIP-PLGA-MS were implanted after 2h of infection in the Femur fracture site of rats in group A and group B respectively after debridement. After 28 days of treatment, the rats were analyzed with X ray and microbiological assay. Results CIP-PLGA-MS between the size ranges of 30-100 μm were obtained. The production yields, drug content and encapsulation efficiencies were 71.37%, 4.82% and 13.75% respectively. In vitro drug release studies shown that these microspheres had significant burst release and their 28 days drug cumulative release rate was up to 71.8%. Based on the in vivo data, cure rate of the rats implanted with CIP-PLGA-MS and empty microspheres were 94.44% and 61.11% respectively (P<0.05). Conclusion CIP-PLGA-MS were found to be effective for the treatment of Gustilo Ⅱ type open fracture in an animal experimental model. Therefore, these microspheres may be potentially useful in clinical medicine.