Li Min, Lv Li, Guo Aijie, Shen Yuanyuan, Guo Shengrong
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
J Nanosci Nanotechnol. 2018 Mar 1;18(3):1585-1593. doi: 10.1166/jnn.2018.10845.
Curcumin (Cur) has potent antitumor activity; however, its clinical use is limited due to its hydrophobicity and instability at physiological pH. In this work, Cur was incorporated into MPEG2K-P(CL-co-LLA) micelles to form the Cur-loaded micelles with drug loadings from 4.72% to 35.21% depending on the ratios of drug to MPEG2K-P(CL-co-LLA). The resulting Cur-loaded micelles were spherical with mean hydrodynamic diameters in the range of 28.8 to 58.6 nm, having excellent water-solubility and good stability at pH 7.4. The freeze-drying powders of the Cur-loaded micelles were easily rehydrated. It was found that Cur was slowly released from the micelles with a cumulative drug release percentage of 78.11% within 14 days and there was no obvious drug burst release. MTT tests showed that, the IC50 values of the Cur-loaded micelles were lower than those of free Cur against cancer cells (MDA-MB-231 cells and 4T1 cells). No matter for cancer cells (MDA-MB-231 cells and 4T1 cells) or healthy cells (L929 cells), cell viabilities were all >90% after incubating with the blank MPEG2K-P(CL-co-LLA) micelles, even at very high micelle concentration (up to 1000 μg/mL), indicating the blank micelles were of no or extremely low cytotoxicity per se. The Cur-loaded micelles were taken up mainly via endocytosis route and the cellular uptake on 4T1 cells increased with incubation time. They could induce more cell apoptosis compared to free Cur. These results suggested that curcumin-loaded MPEG2K-P(CL-co-LLA) micelles may be a potential nanoscale drug delivery system for cancer therapy.
姜黄素（Cur）具有强大的抗肿瘤活性；然而，由于其疏水性以及在生理pH值下的不稳定性，其临床应用受到限制。在本研究中，将Cur载入MPEG2K-P(CL-co-LLA)胶束中，根据药物与MPEG2K-P(CL-co-LLA)的比例，形成载药量为4.72%至35.21%的载Cur胶束。所得载Cur胶束呈球形，平均流体动力学直径在28.8至58.6nm范围内，具有优异的水溶性且在pH 7.4时稳定性良好。载Cur胶束的冻干粉末易于复水。结果发现，Cur从胶束中缓慢释放，14天内药物累积释放率为78.11%，且无明显的药物突释现象。MTT试验表明，载Cur胶束对癌细胞（MDA-MB-231细胞和4T1细胞）的IC50值低于游离Cur。无论对于癌细胞（MDA-MB-231细胞和4T1细胞）还是健康细胞（L929细胞），与空白MPEG2K-P(CL-co-LLA)胶束孵育后，细胞活力均>90%，即使在非常高的胶束浓度（高达1000μg/mL）下，这表明空白胶束本身无细胞毒性或细胞毒性极低。载Cur胶束主要通过内吞途径被摄取，且对4T1细胞的细胞摄取量随孵育时间增加。与游离Cur相比，它们可诱导更多细胞凋亡。这些结果表明，载姜黄素的MPEG2K-P(CL-co-LLA)胶束可能是一种潜在的用于癌症治疗的纳米级药物递送系统。
