Department of Materials Science and Biotechnology, Graduate School of Science and Engineering, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime 790-8577, Japan.
Int J Pharm. 2010 Apr 15;389(1-2):157-67. doi: 10.1016/j.ijpharm.2010.01.033. Epub 2010 Jan 25.
The lectin Eucheuma serra agglutinin (ESA) is known from previous studies to specifically bind to high-mannose type N-glycans and to induce apoptotic cancer cell death in vitro. In this study, Span 80 vesicles, with an average diameter between about 200 and 400 nm, containing immobilized ESA were prepared from the nonionic surfactant Span 80, also known as sorbitan monooleate. The vesicles were investigated in vitro and in vivo to evaluate the vesicles's potential applicability as novel drug delivery system. The results obtained are promising since the following was observed: (i) vesicular ESA had the same hemagglutinating activity as free ESA, demonstrating its biological activity when bound to the vesicles; (ii) vesicles containing immobilized ESA decreased the viability of Colo201 cancer cells in vitro while the growth of normal cells was not affected; (iii) the vesicles showed binding to Colo201 cells in vitro and caused inhibition of cancer cell growth in nude mice to which the vesicle-treated cells were added; (iv) the vesicles diminished tumor growth after intravenous administration to nude mice which contained an implanted Colo201 tumor; (v) the vesicles showed a tendency to accumulate at the site of the tumor 6h after i.v. administration to nude mice. Thus, all measurements carried out indicate that this type of Span 80 vesicle can be considered as promising alternatives to conventional phospholipid-based vesicles.
从先前的研究中可知，凝集素 Eucheuma serra 凝集素（ESA）特异性结合高甘露糖型 N-聚糖，并在体外诱导癌细胞凋亡。在这项研究中，从非离子表面活性剂山梨醇单油酸酯（也称为 Span 80）制备了平均直径在 200 至 400nm 之间的含有固定化 ESA 的 Span 80 囊泡。在体外和体内研究了这些囊泡，以评估它们作为新型药物递送系统的潜在适用性。所获得的结果是有希望的，因为观察到以下几点：（i）囊泡 ESA 具有与游离 ESA 相同的血凝活性，表明其在与囊泡结合时具有生物活性；（ii）含有固定化 ESA 的囊泡降低了 Colo201 癌细胞的体外活力，而正常细胞的生长不受影响；（iii）囊泡在体外与 Colo201 细胞结合，并导致添加了囊泡处理细胞的裸鼠中癌细胞生长受到抑制；（iv）囊泡在含有植入的 Colo201 肿瘤的裸鼠中静脉给药后减少了肿瘤生长；（v）囊泡在静脉给药后 6 小时向裸鼠的肿瘤部位有聚集的趋势。因此，所有进行的测量都表明，这种类型的 Span 80 囊泡可以被认为是传统基于磷脂的囊泡的有前途的替代品。
