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首页> 外文期刊>Cancer letters >Proapoptotic miltefosine nanovesicles show synergism with paclitaxel: Implications for glioblastoma multiforme therapy
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Proapoptotic miltefosine nanovesicles show synergism with paclitaxel: Implications for glioblastoma multiforme therapy

机译:促凋亡的米特磷碱纳米囊泡与紫杉醇显示协同作用:对胶质母细胞瘤多形疗法的影响

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Hexadecylphosphocholine (HePC) or miltefosine based proapoptotic lipid nanovesicles encapsulating paclitaxel for synergistic anticancer effect of paclitaxel and miltefosine in chemoresistant human glioblastoma multiforme (U-87 MG) overexpressing multidrug resistance 1 (MDR1) gene product P-glycoprotein (P-gp), were developed in this study. The nanovesicles had 100-200nm size and a negative zeta potential (~-25mV) and optimized for miltefosine content based on their physiochemical properties. With a high encapsulation efficiency of 94%, the nanovesicles showed sustained release of paclitaxel in nasal fluid and triggered release in the cerebrospinal fluid. Synergistic action of paclitaxel and miltefosine was observed with a low IC50 of 162±5nM. The nanovesicle also overcame drug resistance and showed ATP dependent uptake via clathrin mediated pathway in glioblastoma cells. An improved therapeutic efficacy in comparison to Taxol?, the current clinical formulation of paclitaxel was observed. Efficient brain uptake of the nanovesicles upon intranasal administration was observed in vivo and the nanovesicles were also found to be able to cross blood brain barrier. These studies therefore suggest the therapeutic potential of proapoptotic lipid nanovesicles and their feasibility for intranasal administration in the treatment of chemoresistant glioblastoma.
机译:六聚磷酸胆碱(HePC)或基于紫杉醇的促凋亡脂质纳米囊泡包裹紫杉醇,用于紫杉醇和miltefosine在过表达多药耐药性1(MDR1)的化学耐药性人成胶质细胞瘤(U-87 MG)中的协同抗癌作用,P糖蛋白是P-糖蛋白在这项研究中开发。纳米囊泡的大小为100-200nm,ζ电位为负(〜-25mV),并根据其理化性质对米替福辛含量进行了优化。纳米囊泡具有94%的高封装效率,可在鼻液中持续释放紫杉醇,并在脑脊液中触发释放。紫杉醇和米替福星具有协同作用,IC50低至162±5nM。纳米囊泡还克服了耐药性,并在胶质母细胞瘤细胞中通过网格蛋白介导的途径显示出ATP依赖性摄取。与紫杉醇的当前临床配方相比,紫杉醇具有更好的治疗效果。在体内鼻内给药后,观察到纳米囊泡对脑的有效摄取,并且还发现该纳米囊泡能够穿越血脑屏障。因此,这些研究提示了促凋亡脂质纳米囊的治疗潜力及其在鼻内给药治疗化学耐药性胶质母细胞瘤中的可行性。

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