In vitro and in vivo anti-tumor effects of novel Span 80 vesicles containing immobilized Eucheuma serra agglutinin

In vitro and in vivo anti-tumor effects of novel Span 80 vesicles containing immobilized Eucheuma serra agglutinin
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DOI:
10.1016/j.ijpharm.2010.01.033
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发表时间:
2010-04-15
影响因子:
5.8
通讯作者:
Kato, Keiichi
Kato, Keiichi
中科院分区:
医学2区
文献类型:
--
作者:
Omokawa, Yousuke;Miyazaki, Tatsuhiko;Kato, Keiichi

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从先前的研究中已知凝集素麒麟菜凝集素(ESA)特异性结合高甘露糖型N-聚糖并在体外诱导凋亡性癌细胞死亡。在这项研究中,Span 80囊泡,具有约200和400 nm之间的平均直径,含有固定化的ESA从非离子表面活性剂Span 80,也称为脱水山梨糖醇单油酸酯制备。对该囊泡进行了体内外研究,以评价其作为新型药物传递系统的潜在应用性。获得的结果很有希望,因为观察到以下情况:(i)囊泡ESA具有与游离ESA相同的血凝活性,证明其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Colo 201癌细胞的活力体外,而正常细胞的生长不受影响;(iii)所述囊泡在体外显示出与Colo 201细胞的结合,并且在加入囊泡处理的细胞的裸鼠中引起癌细胞生长的抑制;(iv)所述囊泡在静脉内施用至含有植入的Colo 201肿瘤的裸鼠后减少肿瘤生长;(v)iv后6 h,囊泡显示出在肿瘤部位积聚的趋势。给药至裸鼠。因此,进行的所有测量表明,这种类型的Span 80囊泡可以被认为是传统的磷脂基囊泡的有前途的替代品。(C)2010爱思唯尔有限公司版权所有。
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 6 h after iv. 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. (C) 2010 Elsevier B.V. All rights reserved.