Alomrani Abdullah, Badran Mohamed, Harisa Gamaleldin I, ALshehry Mohamed, Alhariri Moayed, Alshamsan Aws, Alkholief Musaed
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, P.O. Box 2457, Saudi Arabia.
Nanobiotechnology Unit, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Saudi Pharm J. 2019 Jul;27(5):603-611. doi: 10.1016/j.jsps.2019.02.008. Epub 2019 Mar 1.
Surface-coated nanocarriers have been extensively used to enhance the delivery of anticancer drugs and improve their therapeutic index. In this study, chitosan (CS)-coated flexible liposomes (chitosomes) containing 5-fluorouracil (5-FU) were designed and characterized for use as a novel approach to target colon cancer cells. 5-FU-loaded flexible liposomes (F1, F2, and F3) and 5-FU-loaded chitosomes (F4, F5, and F6) were prepared using film hydration and electrostatic deposition techniques, respectively. The particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), morphology, and drug release ability, and cytotoxicity of the formulations were determined. The results revealed that the size of chitosomes ranged from 212 to 271 nm with a positive surface charge of 6.1 to 14.7 mV, whereas the particle size of liposomes ranged from 108 to 234 nm with negative surface charges of -2.3 to -16.3. F3 and F6 had a spherical shape with a rough surface structure. The drug release study revealed that chitosomes retard 5-FU release as opposed to the 5-FU solution and liposomes. The cytotoxicity study using a colon cancer cell line (HT-29) showed that 5-FU-loaded chitosomes were more effective in killing cancer cells in a sustained manner than liposomes and the 5-FU solution. Chitosomes were therefore successfully developed as nanocarriers of 5-FU, with potential cytotoxicity for colorectal cancer cells.
表面包覆的纳米载体已被广泛用于增强抗癌药物的递送并提高其治疗指数。在本研究中，设计并表征了含有5-氟尿嘧啶（5-FU）的壳聚糖（CS）包覆的柔性脂质体（壳聚糖脂质体），作为靶向结肠癌细胞的一种新方法。分别采用薄膜水化法和静电沉积技术制备了载有5-FU的柔性脂质体（F1、F2和F3）和载有5-FU的壳聚糖脂质体（F4、F5和F6）。测定了制剂的粒径、多分散指数（PDI）、zeta电位、包封率（EE%）、形态、药物释放能力和细胞毒性。结果显示，壳聚糖脂质体的粒径范围为212至271 nm，表面正电荷为6.1至14.7 mV，而脂质体的粒径范围为108至234 nm，表面负电荷为-2.3至-16.3。F3和F6呈球形，表面结构粗糙。药物释放研究表明，与5-FU溶液和脂质体相比，壳聚糖脂质体延缓了5-FU的释放。使用结肠癌细胞系（HT-29）进行的细胞毒性研究表明，载有5-FU的壳聚糖脂质体在持续杀死癌细胞方面比脂质体和5-FU溶液更有效。因此，壳聚糖脂质体已成功开发为5-FU的纳米载体，对结肠直肠癌细胞具有潜在的细胞毒性。
