范子梁，金冰慧，徐霞芳，蒋巧颖，徐荷林

    (温州医科大学 药学院，浙江 温州 325035)

    ·论 著·

    包载姜黄素纳米胶束的制备与体外抗肿瘤评价

    范子梁，金冰慧，徐霞芳，蒋巧颖，徐荷林

    (温州医科大学 药学院，浙江 温州 325035)

    目的：构建载姜黄素纳米胶束，体外评价其对C6脑胶质瘤细胞的生长抑制作用。方法：合成新型十一烯酸-接枝-ε-多聚赖氨酸(ε-PLL-UNA)聚合物，并对其结构进行表征，采用芘荧光探针法对其临界胶束浓度进行测定；以ε-PLL-UNA为材料，采用透析法制备载姜黄素纳米胶束，以动态光散射和透射电镜对其粒径、形态进行表征，以动态透析法测定药物释放行为，以激光共聚焦显微镜观察体外细胞摄取性，以肿瘤球模型考察其体外抗肿瘤作用。结果：1H-NMR和FT-IR结果表明ε-PLL-UNA聚合物成功合成，其临界胶束浓度为0.19 g/L，能自发组装成胶束；载姜黄素纳米胶束载药量能达到12.22%±2.13%、包封率则高达85.12%±3.64%，平均粒径为(60.6±2.1)nm、Zeta电位为(28.2±5.6)mV，具有球形微观结构；该纳米胶束48 h释放84%的姜黄素，体外快速被C6细胞摄取；与姜黄素溶液相比，该纳米胶束能明显抑制胶质瘤细胞球的生长。结论：ε-PLL-UNA聚合物胶束对姜黄素具有较高的载药量，粒径小于100 nm、分布均匀，体外缓慢释放药物，提高了C6细胞对姜黄素的摄取，而且对C6细胞球具有有效的杀伤作用。

    姜黄素；胶束；聚赖氨酸；十一烯酸；神经胶质瘤；细胞球

    Abstract: Objective:To prepare a novel polymer micelles encapsulating curcumin (CUR) and evaluate its anti-tumor effect on glioma in vitro.Methods:A novel polymer, undecenoic acid-grafted-ε-polylysine (ε-PLLUNA), was synthesized, and its chemical structure was confirmed by1H-NMR and FT-IR. The CAC value of ε-PLL-UNA polymer was also detected by pyrene fluorescence probe. CUR-loaded micelle was prepared by dialysis method using ε-PLL-UNA as materials, and its particle size and morphology were also studied under dynamic light scattering (DLS) and transmission electron microscope (TEM), respectively. Furthermore, in vitro drug release profiles from CUR-Micelles were explored by dynamic dialysis method. Finally, the cellular toxicity against C6 cells spheroids and the cellular uptake of CUR-Micelles were evaluated.Results:ε-PLL-UNA polymer was successfully synthesized and able to self-assemble into micelles above its CAC value of 0.19 g/L. CUR-loaded micelle had a mean diameter of (60.6±2.1)nm, and zeta potential of (28.2±5.6)mV, exhibiting the spherical shape determined by TEM. Drug loading content and drug loading efficiency for CUR-loaded micelle were high up to 12.22%±2.13% and 85.12%±3.64%, respectively. About 84% of CUR were released from the micelles in 48 hours. CUR-loaded micelle can promote the cellular uptake of its encapsulated CUR by C6 cells, displaying a significantly higher cytotoxicity against C6 cells. Besides, the growth of C6 cells spheroids was significantly inhibited by CUR-loaded micelle.Conclusion:CUR is efficiently encapsulated in ε-PLL-UNA micelles with a particle size of less than 100 nm, which improved the cellular uptake of C6 cells. The sustained-release of CUR from CUR-loaded micelle is also observed. More importantly, CUR-Micelles has superior growth inhibition against C6 cells spheroids. ......