Foote MaryAnn
MA Foote Associates, 4284 Par Five Court, Westlake Village, CA 91362, USA.
Biotechnol Annu Rev. 2007;13:345-57. doi: 10.1016/S1387-2656(07)13012-X.
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.
纳米技术是指使用非常小的物质碎片,其直径通常≤200纳米。纳米白蛋白结合型(nab)紫杉醇是细胞毒素紫杉醇的一种可溶形式,已在癌症化疗中显示出效用,它是通过使用蛋白质白蛋白的nab技术生产的。nab-紫杉醇靶向肿瘤,通过白蛋白受体介导的(gp60)内皮细胞转胞吞作用这一新型机制增强肿瘤渗透,并避免使用诸如聚氧乙烯蓖麻油和吐温等表面活性剂和溶剂。nab-紫杉醇将与聚氧乙烯蓖麻油相关的毒性降至最低,并消除了对聚氧乙烯蓖麻油引起的过敏反应进行预处理的必要性。围绕活性药物的白蛋白涂层有助于将纳米颗粒转运至肿瘤细胞内部,肿瘤细胞通过gp60途径优先摄取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-紫杉醇在肿瘤内达到了更高的浓度,并通过消除紫杉醇在血浆中的滞留提高了紫杉醇的生物利用度。与溶剂型紫杉醇相比,在等效毒性剂量下,nab-紫杉醇产生了更完全的肿瘤消退、更长的复发时间、更长的倍增时间和更长的生存期。在晚期实体瘤患者的临床试验中,nab-紫杉醇已被证明与溶剂型紫杉醇相比具有更高的疗效,且无需预处理。nab-紫杉醇对先前化疗无效的患者也有效。nab技术有应用于其他不溶性药物的潜力。