氧化还原敏感PEO-PPO-SS-DTX聚合物胶束的构建及体外抗肿瘤评价

doi:10.6040/j.issn.1671-7554.0.2018.190

摘要/Abstract

摘要： 目的合成聚氧乙烯-聚氧丙烯(PEO-PPO)-SS-多西他赛(DTX)接枝物,并对其进行表征和体外评价。方法合成PEO-PPO-SS-DTX接枝物,利用核磁共振氢谱(¹H-NMR)与傅里叶变换红外光谱(FT-IR)对其分子结构进行确证。制备PEO-PPO-SS-DTX胶束,研究PEO-PPO-SS-DTX接枝物在水溶液中的组装行为。利用动态光散射仪测其粒径,荧光法测其临界胶束浓度(CMC),紫外分光光度法测其载药量(DL)与溶血率(HR)。利用体外细胞毒性实验与细胞摄取实验对其进行体外评价。结果成功合成了PEO-PPO-SS-DTX接枝物,并成功制备了PEO-PPO-SS-DTX胶束。PEO-PPO-SS-DTX接枝物可以在水溶液中自发组装成球形胶束。粒径平均值为(159.0±4.4)nm,多分散系数(PDI)为0.18±0.01,CMC为5.0 μg·mL^-1,DL为8.3%,HR<5%。体外细胞毒性与细胞摄取实验结果表明,PEO-PPO-SS-DTX胶束对Hep1-6细胞具有很好的抗肿瘤活性与摄取率。结论 PEO-PPO-SS-DTX接枝物各方面性能良好,具有很好的应用前景。

关键词: 氧化还原敏感, PEO-PPO-SS-DTX接枝物, 聚合物胶束, 抗肿瘤评价

Abstract: Objective To synthesize, characterize and evaluate allyl polyoxyethylene-polyethylene oxide(PEO-PPO)-SS-docetaxel(DTX)conjugate. Methods The PEO-PPO-SS-DTX conjugate was synthesized and confirmed structurally by nuclear magnetic resonance hydrogen spectrum(¹H-NMR)and fourier transform infrared spectroscopy(FT-IR). Then the PEO-PPO-SS-DTX micelles were prepared and the assembly behavior of the PEO-PPO-SS-DTX conjugate in aqueous solution was studied. The average size of the micelles, critical micelle concentration(CMC), and drug loading(DL)content and hemolysis rate(HR)were measured by dynamic light scattering instrument, fluorescence, and UV spectrophotometry, respectively. The cytotoxicity experiment and cell uptake experiment were used to evaluate its in vitro anticancer efficacy. Results The PEO-PPO-SS-DTX conjugate and micelles were prepared successfully. The PEO-PPO-SS-DTX conjugate could assemble into the spherical micelles spontaneously in aqueous solution. The average size of the micelles was(159.0±4.4)nm with poly dispersity index(PDI)of 0.18±0.01. The CMC was about 5.0 μg·mL^-1, drug loading(DL)content was 8.3%, and the hemolysis rate(HR)was less than 5%. The PEO-PPO- 山东大学学报 (医学版)56卷6期 -刘新,等.氧化还原敏感PEO-PPO-SS-DTX聚合物胶束的构建及体外抗肿瘤评价 \=-SS-DTX micelles had excellent anti-tumor efficiency and cell uptake rate against Hep1-6 cells. Conclusion The PEO-PPO-SS-DTX conjugate has excellent properties and great potentical for clinical application.

Key words: Redox-sensitivity, PEO-PPO-SS-DTX conjugate, Polymer micelles, Antitumor evaluation

中图分类号:

R944

刘新,张佩,何文秀,栾玉霞. 氧化还原敏感PEO-PPO-SS-DTX聚合物胶束的构建及体外抗肿瘤评价[J]. 山东大学学报 (医学版), 2018, 56(6): 13-20.

LIU Xin, ZHANG Pei, HE Wenxiu, LUAN Yuxia. Construction and in vitro anticancer evaluation of redox-sensitive polymeric micelles based on PEO-PPO-SS-DTX conjugate[J]. Journal of Shandong University (Health Sciences), 2018, 56(6): 13-20.

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