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新型利福平缓释植入支架材料的制备及体内缓释分析

摘要:目的 制备一种可局部植入的具有良好的药物缓释以及成骨性能的新型材料并验证其缓释性能和生物安全性。方法 使用乳化溶媒挥发法制备利福平-聚乳酸羟基乙酸共聚物载药微球并将其与带负电荷硫酸钙/β-磷酸三钙复合骨水泥结合制备成一种新型的复合抗结核支架材料。分别观察微球以及复合支架材料的体外缓释性能。通过在成年雄性SD大鼠的肌袋模型中植入复合抗结核支架材料来观察不同时间点的局部药物浓度以及血药浓度,通过血生化指标以及肝脏病理组织切片评价复合抗结核支架材料的体内安全性。结果 利福平/聚乳酸羟基乙酸共聚物载药微球的包封率和载药率分别为(56.05±5.33)%和(29.80±2.88)%。在第28天微球和复合支架材料的体外累积释放率分别为(94.19±5.40)%和(82.23±6.28)%。局部植入抗结核复合支架材料后药物缓释效果令人满意,在术后第28天局部药物浓度仍可达到(16.18±0.35)µg/g。血浆生化指标提示局部植入抗结核复合支架材料后会出现一过性肝损伤,肝脏病理切片的结果显示在第28天肝损伤基本得到完全修复。结论 利福平-聚乳酸羟基乙酸共聚物载药微球-带负电荷硫酸钙/β-磷酸三钙复合骨水泥作为一种新型的抗结核局部植入物,具有良好的缓释效果以及生物相容性,能弥补传统抗结核疗法局部药物浓度过低的不足。

英文摘要:Objective To fabricate a new composite scaffold material as an implant for sustained delivery of rifampicin and evaluate its performance of sustained drug release and biocompatibility. Methods The composite scaffold material was prepared by loading poly(lactic-co-glycolic) acid (PLGA) microspheres that encapsulated rifampicin in a biphasic calcium composite material with a negative surface charge. The in vitro drug release characteristics of the microspheres and the composite scaffold material were evaluated; the in vivo drug release profile of the composite scaffold material implanted in a rat muscle pouch was evaluated using high-performance liquid chromatography. The biochemical parameters of the serum and liver histopathologies of the rats receiving the transplantation were observed to assess the biocompatibility of the composite scaffold material. Results The encapsulation efficiency and drug loading efficiency of microspheres were (56.05±5.33)% and (29.80±2.88)%, respectively. The cumulative drug release rate of the microspheres in vitro was (94.19±5.4)% at 28 days, as compared with the rate of (82.23±6.28)% of composite scaffold material. The drug-loaded composite scaffold material showed a good performance of in vivo drug release in rats, and the local drug concentration still reached 16.18±0.35 μg/g at 28 days after implantation. Implantation of the composite scaffold material resulted in transient and reversible liver injury, which was fully reparred at 28 days after the implantation. Conclusion The composite scaffold material possesses a good sustained drug release capacity and a good biocompatibility, and can serve as an alternative approach to conventional antituberculous chemotherapy.

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[V1] 2017-12-27 12:40:26 chinaXiv:201712.01036V1 下载全文
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