利用纳米技术改善抗肿瘤药物的特性:与溶剂型紫杉醇相比,nab-紫杉醇的特性得到了改善。

MaryAnn Foote
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引用次数: 50

摘要

纳米技术指的是使用非常小的物质,通常直径小于或等于200纳米。纳米颗粒白蛋白结合(nab)紫杉醇是细胞毒素紫杉醇的一种可溶性形式,已被证明在癌症化疗中具有实用性,它是由nab技术利用蛋白白蛋白生产的。nab-紫杉醇靶向肿瘤,通过白蛋白受体介导(gp60)内皮细胞吞噬的新机制增强肿瘤穿透,避免使用表面活性剂和溶剂,如Cremophor和Tween。nab-紫杉醇将与cremoophor相关的毒性降至最低,并消除了对cremoophor引起的超敏反应的预用药需求。包裹在活性药物周围的白蛋白涂层有助于纳米颗粒运输到肿瘤细胞内部,通过gp60途径优先吸收白蛋白作为营养物质。在非临床研究中,与溶剂型紫杉醇相比,nab-紫杉醇获得了更高的肿瘤内浓度,并通过消除血浆中紫杉醇的夹带提高了紫杉醇的生物利用度。与溶剂型紫杉醇相比,在等量剂量下,nab-紫杉醇的回归更完全,复发时间更长,翻倍时间更长,生存期更长。在晚期实体瘤患者的临床试验中,与溶剂型紫杉醇相比,nab-紫杉醇在不需要预用药的情况下具有优越的疗效。nab-紫杉醇对既往化疗无效的患者有效。nab技术有可能应用于其他不溶性药物。
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Using nanotechnology to improve the characteristics of antineoplastic drugs: improved characteristics of nab-paclitaxel compared with solvent-based paclitaxel.

Nanotechnology refers to the use of very small pieces of matter, typically < or =200 nm in diameter. Nanoparticle albumin-bound (nab) paclitaxel, a soluble form of the cytotoxin paclitaxel that has demonstrated utility in the setting of cancer chemotherapy, is produced by nab technology using the protein albumin. nab-Paclitaxel targets tumors, enhances tumor penetration by the novel mechanism of albumin receptor-mediated (gp60) endothelial transcytosis, and avoids the use of surfactants and solvents such as Cremophor and Tween. nab-Paclitaxel minimizes the toxicities associated with Cremophor and eliminates the need for premedication for hypersensitivity reactions caused by Cremophor. The albumin coating that surrounds the active drug assists in the transport of the nanoparticles to the interior of the tumor cell that preferentially takes in albumin as a nutrient through the gp60 pathway. In nonclinical studies, nab-paclitaxel achieved higher intratumoral concentrations compared with solvent-based paclitaxel and increased the bioavailability of paclitaxel by eliminating the entrapment of paclitaxel in the plasma. Compared with solvent-based paclitaxel, at equitoxic doses, the nab-paclitaxel produced more complete regressions, longer time to recurrence, longer doubling times, and prolonged survival. nab-Paclitaxel has been shown to have superior efficacy compared with solvent-based paclitaxel without the need for premedication in clinical trials of patients with advanced solid tumors. nab-Paclitaxel has been effective in patients for whom previous chemotherapy has not been helpful. nab Technology has the potential to be applied to other insoluble drugs.

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