Wang Wen-Yan, Cao Yun-Xia, Zhou Xiao, Wei Bing
Department of Obstetrics and Gynecology, The Second Hospital of Anhui Medical University, Hefei, Anhui, 230601, People's Republic of China.
Teaching and Research Group of Obstetrics and Gynecology, Anhui Medical University, Hefei, Anhui, 230032, People's Republic of China.
Drug Des Devel Ther. 2019 Jul 4;13:2205-2213. doi: 10.2147/DDDT.S205787. eCollection 2019.
In this study, novel folic acid (FA)-modified curcumin (CUR) liposomes (LPs) were developed and evaluated for their antitumor activity in vitro and in vivo. Characterization of the LPs, including transmission electron microscopy, morphology, particle size, and zeta potential studies, was carried out. Drug entrapment efficiency, drug-loading capacity, and release properties in vitro were tested. The in vitro growth inhibition activity, cellular uptake efficiency, and cell apoptosis of FA-modified CUR LPs were also investigated by a cervical cancer HeLa cell model. The optimized distearoyl-l-a-phosphatidylethanolamine (DSPE)-PEG-FA-LPs/CUR formed spherical vesicles of nanometer sizes and had particle sizes of 112.3±4.6 nm, polydispersity index of 0.19±0.03, and zeta potential of -15.3±1.4 mV. In addition, the EE% and DL% of (DSPE)-PEG-FA-LPs/CUR were 87.6% and 7.9%, respectively. Compared with the free drug, FA-modified CUR LPs had sustained-release properties in vitro. In vivo, a strong green fluorescence was observed in the cytoplasmic region after incubation of (DSPE)-PEG-FA-LPs/CUR for 2 hrs. (DSPE)-PEG-FA-LPs/CUR showed a superior antiproliferative effect on HeLa cells and had a better antitumor effect in vivo than the non-modified LPs. These results indicated that (DSPE)-PEG-FA-LPs/CUR was a promising candidate for antitumor drug delivery.
在本研究中，制备了新型叶酸（FA）修饰的姜黄素（CUR）脂质体（LPs），并对其体外和体内抗肿瘤活性进行了评估。对LPs进行了表征，包括透射电子显微镜、形态、粒径和zeta电位研究。测试了体外药物包封率、载药量和释放特性。还通过宫颈癌HeLa细胞模型研究了FA修饰的CUR LPs的体外生长抑制活性、细胞摄取效率和细胞凋亡。优化后的二硬脂酰-l-α-磷脂酰乙醇胺（DSPE）-聚乙二醇（PEG）-FA-LPs/CUR形成了纳米尺寸的球形囊泡，粒径为112.3±4.6 nm，多分散指数为0.19±0.03，zeta电位为-15.3±1.4 mV。此外，（DSPE）-PEG-FA-LPs/CUR的包封率（EE%）和载药量（DL%）分别为87.6%和7.9%。与游离药物相比，FA修饰的CUR LPs在体外具有缓释特性。在体内，（DSPE）-PEG-FA-LPs/CUR孵育2小时后，在细胞质区域观察到强烈的绿色荧光。（DSPE）-PEG-FA-LPs/CUR对HeLa细胞显示出优异的抗增殖作用，并且在体内比未修饰的LPs具有更好的抗肿瘤效果。这些结果表明，（DSPE）-PEG-FA-LPs/CUR是一种有前途的抗肿瘤药物递送候选物。
