Wang Yu-Chi, Bai Meng-Yi, Yeh Ying-Ting, Tang Sung-Ling, Yu Mu-Hsien
Department of Obstetric and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 10607, Taiwan.
Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan.
Polymers (Basel). 2020 Feb 20;12(2):479. doi: 10.3390/polym12020479.
Levamisole (LEVA) is used to treat worm infections, but it can also inhibit cancer cell growth by inhibiting the aldehyde dehydrogenase pathway. Therefore, here, we developed a drug carrier targeting CD133, a biomarker overexpressed in ovarian cancer cells. The particle structure and cytotoxicity of the prepared LEVA-containing particles-called LEVA/PVP/PMMA microparticles (MPs) (because it used matrix material polyvinylpyrrolidone (PVP) and poly(methylmethacrylate) (PMMA))-were investigated in the ovarian cancer cell lines SKOV-3 and CP70. The particle size of the MPs was determined to be 1.0-1.5 µm and to be monodispersed. The hydrophilic property of PVP created a porous MP surface after the MPs were soaked in water for 20 min, which aided the leaching of the hydrophilic LEVA out of the MPs. The encapsulation efficiency of LEVA/PVP/PMMA MPs could reach up to 20%. Free-form LEVA released 50% of drugs in <1 h and 90% of drugs in 1 day, whereas the drug release rate of LEVA/PVP/PMMA MPs was much slower; 50% released in 4 h and only 70% of drugs released in 1 day. In the in vitro cell model test, 5 mM free-form LEVA and 0.1 g/mL CD133 targeted LEVA/PVP/PMMA MPs reduced SKOV-3 cell viability by 60%; 0.1 g/mL LEVA/PVP/PMMA MPs was equivalent to a similar dosage of the free drug. In addition, the cytotoxicity of CD133-conjugated LEVA/PVP/PMMA MPs shows a different cytotoxicity response toward cell lines. For SKOV-3 cells, treatment with free-form LEVA or CD133-conjugated LEVA/PVP/PMMA MPs exerted dose-dependent cytotoxic effects on SKOV-3 cell viability. However, CD133-conjugated LEVA/PVP/PMMA MPs demonstrated no significant dose-dependent cytotoxic efficacy toward CP70 cells.
左旋咪唑（LEVA）用于治疗蠕虫感染，但它也可以通过抑制醛脱氢酶途径来抑制癌细胞生长。因此，在此我们开发了一种靶向CD133的药物载体，CD133是一种在卵巢癌细胞中过表达的生物标志物。在卵巢癌细胞系SKOV-3和CP70中研究了制备的含LEVA颗粒（称为LEVA/PVP/PMMA微粒（MPs），因为它使用了基质材料聚乙烯吡咯烷酮（PVP）和聚甲基丙烯酸甲酯（PMMA））的颗粒结构和细胞毒性。MPs的粒径测定为1.0 - 1.5 µm且为单分散。MPs在水中浸泡20分钟后，PVP的亲水性使MP表面形成多孔结构，这有助于亲水性的LEVA从MPs中浸出。LEVA/PVP/PMMA MPs的包封率可达20%。游离形式的LEVA在<1小时内释放50%的药物，在1天内释放90%的药物，而LEVA/PVP/PMMA MPs的药物释放速率要慢得多；4小时内释放50%，1天内仅释放70%的药物。在体外细胞模型试验中，5 mM游离形式的LEVA和0.1 g/mL靶向CD133的LEVA/PVP/PMMA MPs使SKOV-3细胞活力降低60%；0.1 g/mL LEVA/PVP/PMMA MPs相当于类似剂量的游离药物。此外，CD133偶联的LEVA/PVP/PMMA MPs的细胞毒性对细胞系表现出不同的细胞毒性反应。对于SKOV-3细胞，用游离形式的LEVA或CD133偶联的LEVA/PVP/PMMA MPs处理对SKOV-3细胞活力产生剂量依赖性细胞毒性作用。然而，CD133偶联的LEVA/PVP/PMMA MPs对CP70细胞未显示出显著剂量依赖性细胞毒性功效。
