Abstract

This study aimed to synthesize Melphalan (MEL)-loaded PEGylated nanoliposomes and evaluate their cytotoxic effects on ovarian cancer A2780CP and SKOV3 cells. For this purpose, MEL-loaded PEGylated nanoliposomes were prepared by the reverse-phase evaporation method. They were then characterized, and the results showed that the size, size distribution, and zeta potential of the nanoformulation were 129.1 ± 5.5 nm, 0.240 ± 0.13, and −18.9 $\pm$ 0.31 mv, respectively. Also, the encapsulation and loading efficiencies of MEL in the nanoparticles were determined to be 98.3 ± 2.1% and 5.2 ± 1.3%, respectively. Also, the drug release pattern was evaluated using a dialysis bag method, and the results demonstrated that 20.5% of MEL was released after 48 h from the nanoparticles, which was 2.7-fold slower compared to when the standard drug was used. In addition, the effects of the standard drug and nanoformulation on cell viability was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the results showed that nanoformulation had 1.4-fold more toxicity than the standard drug. Moreover, the extent of apoptosis was investigated using the Annexin- propidium iodide kit and flow cytometry method. The results showed that MEL-loaded PEGylated nanoliposomes increased the apoptotic cells compared to the control group.

摘要

这项研究旨在合成载有Melphalan（MEL）的PEG化纳米脂质体，并评估其对卵巢癌A2780CP和SKOV3细胞的细胞毒性作用。为此，通过反相蒸发法制备了负载MEL的聚乙二醇化纳米脂质体。然后对其进行表征，结果表明，纳米制剂的尺寸，尺寸分布和Zeta电位分别为129.1±5.5 nm，0.240±0.13和-18.9。 $\pm$ 分别为0.31毫伏。而且，确定的MEL在纳米颗粒中的包封和负载效率分别为98.3±2.1％和5.2±1.3％。此外，使用透析袋法评估了药物释放模式，结果表明，在48小时后，纳米颗粒释放了20.5％的MEL，这比使用标准药物时慢了2.7倍。此外，使用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物（MTT）分析评估了标准药物和纳米制剂对细胞活力的影响，结果表明纳米制剂具有毒性是标准药物的1.4倍。此外，使用膜联蛋白-碘化丙锭试剂盒和流式细胞仪方法研究了细胞凋亡的程度。