阶梯缓释抗结核纳米人工骨复合体的生物安全性研究

目的研究阶梯缓释抗结核纳米人工骨复合体（β-TCP／INH-RFP-PCL／SM-SA）的生物安全性。方法对β-TCP／INH-RFP-PCL／SM-SA复合体进行体外噻唑蓝（M1Tr）细胞毒性实验，动物体内急性全身毒性实验、原发性皮肤刺激实验、皮内刺激实验和致敏实验，并设置对照组进行比较。结果β-TCP／INH-RFP-PCL／SM-SA复合体MTT细胞毒性实验显示人工骨材料组细胞存活率在95％以上，细胞毒性1级。人工骨复合材料浸取液不引起豚鼠过敏。原发性皮肤刺激实验和皮内刺激实验均提示复合材料对兔皮肤、皮内无刺激反应。小鼠尾静脉注射后未出现明显全身毒性反应。结论β-TCP／INH-RFP-PCL／SM-SA无明显细胞毒性，具有良好的细胞相容性，在应用过程中能够降低直接使用抗结核药物所带来的生物毒性。动物全身毒性反应、皮肤／内刺激反应和急性过敏反应提示该材料具有良好的生物安全性。

Biological security of ladder-sustained-release anti-TB drugs artificial composite bone

Objective To investigate the biological security of ladder-sustained-release anti-TB drugs artificial com- posite bone （β-TCP/INH-RFP-PCL/SM-SA）. Methods MTT toxicity test, acute systemic toxicity test, intracutaneous irritation test and skin sensitization in stimulation were performed in the ladder-sustained-release anti-TB drugs artifi- cial composite bone. The results were compared with control group. Results MTT toxicity test showed that the survival rate of bone cells in artificial materials was more than 95% and cytotoxicity was on grade 1. Artificial bone composite material liquid did not cause allergic reaction in guinea pig. Primary skin irritation experiments and intradermal stimu- lation experiment suggested that composite materials to rabbit skin and intracutaneous no stimulation reaction. No obvi- ous systemic toxic reaction was found in mice after intravenous injection. Conclusion There is no MTT cytotoxicity in the ladder-sustained-release anti-TB drugs artificial composite bone. It can reduce the biological toxicity of anti-TB drugs and will not cause systemic toxic reaction, skin/hypodermic stimulation reactions and acute allergic reaction. It has good cell compatibility and biological security.