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Enhanced cytotoxicity of doxorubicin encapsulated in liposomes with reconstituted Sendai F-proteins

机译:增强多柔比星的细胞毒性包封在脂质体中,具有重构的Sendai F-蛋白

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Sendai F -virosomes, a novel type of lipo~me with reconstituted Sendai F - proteins, have been tested as a delivery system for various bioactive materials. However, encapsulation limitations and difficulties in controlling their constituents were draw~cks for further application to therapeutic purposes. We have tried to cpntrol virosomal constit:uents and have enhanced dru~. encapsulation efficiency into the virosomes;In.;'ltro cytotoxicity of doxoFubicin encapsulated in the F -virosomes were compared with free doxorubicin and doxorubicin in conventional liposomes. The £0' -virosomes were spontaneously prepared by detergent dialysis, a reconstitutidn process of Sendai F -proteins into liposomes. The reconstitution density of F -proteins affected the vesicle size of virosomes prepared by detergent dialysis; the larJ;er amount of F -proteins made a smaller size of virosomes. There was littl.e va:riation of size with time at physiological conditions, whilst the vesicle size 6f virosomes increa~eq.'~~...acidic storage conditions (pH 5.5). Doxorubicin encapsulated in the P::virosomes exhibited a lower ICso against B16BL6 mouse melanoma cells and .Ghang human hepatocarcinoma cells than that in conventional liposomes. The F - virosomes also exhibited higher cellular uptake than conventionalliposomes. Addition of dioleoylphophatidylethanolamine, a fusogenic phospholipid, into the F -virosome further increased the cellular uptake as well as in vitro cytotoxicity. These types of viroso'me formulations can be clinically applicable as versatile ves~les for the efficient delivery of various therapeutic drugs, including genetic materials.
机译:Sendai F -Virosomes,一种具有重构仙台F - 蛋白的新型Lipo〜Me,已被测试为各种生物活性材料的输送系统。然而,封装限制和控制其成分的困难是为了进一步应用于治疗目的的CKS。我们已经尝试过cpntrol病毒组群:uents并具有增强的德鲁〜。将效率的效率进入病毒组;在常规脂质体中与自由的多柔比星和多柔比星进行了封装在F -Virosomes中的十字胶质蛋白的Doxofubicin的Ltro细胞毒性。通过洗涤剂透析自发地制备了0英镑的 - virosomes,将仙台F蛋白转化为脂质体的重构丁蛋白。 F蛋白的重构密度影响通过洗涤剂透析制备的病毒组的囊泡尺寸; LARJ; ER数量的F蛋白质的尺寸较小的病毒组。有Littl.e Va:在生理条件下的时间率为时间,囊泡尺寸6f病毒素增量〜eq。'~~ ...酸性储存条件(pH 5.5)。在P ::病毒体中包封的多柔比星,对B16BL6小鼠黑素瘤细胞和.Chang人肝癌细胞表现出低于B16BL6小鼠黑色素瘤细胞。 F - 病毒体还表现出比长锥眼体更高的细胞摄取。添加Diolelylphophatidylidyl醇胺,熔融磷脂,进一步增加了细胞摄取以及体外细胞毒性。这些类型的Vioso'me配方可以临床上适用于多功能Ves 〜LES,以便有效地提供各种治疗药物,包括遗传物质。

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