可降解输尿管支架材料的特性研究

Characterization of biodegradable ureteral scaffold material as drug carrier

目的构建一种生物可降解输尿管载药支架材料,并研究其体内外降解特性、药物释放特性及组织相容性。方法乙交酯-L-丙交酯-ε-己内酯三元无规共聚物材料、雷帕霉素共溶于三氯甲烷溶液中,溶液蒸发法制备两种规格载药支架材料。将材料浸泡于体外尿液环境中,恒温振荡2、4、6、8、10周后,通过大体形态、电镜扫描观察材料的体外降解情况;通过高效液相色谱测定材料载药量变化研究材料药物释放特性。将材料包埋于兔两侧椎旁肌,于1、4、12周时手术取出材料行组织染色切片研究材料的组织相容性。结果体外振荡环境下,4周时管内可见絮状漂浮物,此时质量丢失率约为27%,扫描电镜下材料表面可见细小孔洞,10周时材料降解为泥沙样沉积物。支架载药量逐渐降低,0周组(1 412±28)μg与2周组(1 335±74)μg载药量差异无统计学意义(P>0.05),2周组与4周组(1 165±84)μg、4周组与6周组(622±25)μg、6周组与8周组(286±17)μg载药量差异均有统计学意义(P<0.01)。组织学切片观察急性期表现为手术损伤后炎症反应,植入后期纤维增生不明显。结论新型生物可降解输尿管载药支架材料肌肉包埋组织学反应轻微,具有良好的组织相容性,体外环境下其在降解同时,能持续释放雷帕霉素达8周。

Objective To construct a new biodegradable ureteral scaffold material as drug carrier, and investigate its degradation characteristics, drug-release property and histocompatibility. Methods Two different sizes of ureteral scaffold material for drug carrier were fabricated with polycaprolactone(PCL)/poly(lactic acid-glycolic acid)(PLGA) and rapamycin. General observation and Scanning Electron Microscope(SEM) were performed to investigate the biodegradation characteristics of scaffold materials after 0, 2, 4, 6, 8 and 10 weeks of constant temperature shaking.Meanwhile, scaffold materials were detected by high-performance liquid chromatography(HPLC) to investigate the drug release property. The scaffold materials were implanted in the dorsal muscle of 6 rabbits, and histocompatibility was assessed by histology and image analysis system after 1, 4 and 12 weeks. Results After being dipped in human urine for 4 weeks, a few of floaters could be seen in all centrifuge tube and weight of scaffold materials were decreased by 27%.Under the SEM, small holes were found on the surface of scaffold materials. The drug loading dosage of the scaffolds were gradually decreased, and there were statistically significant differences between every two groups [2 weeks group and 4weeks group of(1 335±74) μg vs(1 165±84) μg, 4 weeks group and 6 weeks group of(1 165±84) μg vs(622±25) μg,6 weeks group and 8 weeks group of(622±25) μg vs(286±17) μg, P<0.01], but not between 0 week group and 2 weeks group [(1 412±28) μg vs(1 335±74) μg, P>0.05]. The results of histology showed mild acute inflammatory reaction, and fibroustissue hyperplasia was proliferated slightly. Conclusion This drug-loading ureteral scaffold material gets along well with body tissues, and the drug is sustainedly released in vitro over 8 weeks.