Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Eur J Pharm Sci. 2018 Mar 1;114:166-174. doi: 10.1016/j.ejps.2017.12.011. Epub 2017 Dec 13.
The aim of this study was to develop a liposomal formulation to selectively target cancer cells. Liposomes were prepared using thin layer method and folic acid (FA) was applied for targeted delivery of 5FU to cancer cells. Liposomes prepared were characterized for encapsulation efficiency (EE%), morphology and their particle size. Cellular uptake, cytotoxicity study and ROS production were evaluated using CT26 cell line. Hemolysis test was performed on rat red blood cells (RBCs). Moreover, the efficacy of targeted liposomes were investigated by in vivo antitumor activity and tissue toxicities were studied by histological examination. The EE% and average particle size of liposomes were 67.88±1.84% and 114.00±4.58nm, respectively. TEM image revealed that liposomes were spherical in shape. Targeted liposomes showed higher cellular uptake, lower IC (12.02μM compared to 39.81μM for liposomal 5FU and 39.81μM for free 5FU) and higher ROS production than free drug (62,271.28 vs 2369.55 fluorescence intensity) on cancer cells. Results of hemolysis assay confirmed the blood biocompatibility of the liposomes. Moreover, folate targeted liposomes showed better tumor inhibition than free drug (88.75mm tumor volume vs 210.00mm) and no tissue abnormalities were found in histological examination. It can be concluded that folate targeted liposomes provide an effective and safe strategy for colon cancer targeted chemotherapy.
本研究旨在开发一种能够选择性靶向癌细胞的脂质体制剂。采用薄膜法制备脂质体，并应用叶酸（FA）将 5FU 靶向递送至癌细胞。对脂质体的包封效率（EE%）、形态和粒径进行了表征。采用 CT26 细胞系评价细胞摄取、细胞毒性研究和 ROS 生成。对大鼠红细胞（RBC）进行溶血试验。此外，通过体内抗肿瘤活性研究了靶向脂质体的疗效，并通过组织学检查研究了组织毒性。脂质体的 EE%和平均粒径分别为 67.88±1.84%和 114.00±4.58nm。TEM 图像显示脂质体呈球形。靶向脂质体在癌细胞中表现出更高的细胞摄取率、更低的 IC（12.02μM 与脂质体 5FU 的 39.81μM 和游离 5FU 的 39.81μM 相比）和更高的 ROS 生成（62,271.28 与游离药物的 2369.55 荧光强度相比）。溶血试验结果证实了脂质体的血液生物相容性。此外，叶酸靶向脂质体的肿瘤抑制作用优于游离药物（肿瘤体积 88.75mm 与 210.00mm 相比），组织学检查未发现组织异常。可以得出结论，叶酸靶向脂质体为结肠癌靶向化疗提供了一种有效且安全的策略。
