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载厄洛替尼白蛋白纳米粒:一种新型的厄洛替尼注射剂型及其对胰腺腺癌ASPC-1和PANC-1细胞系的体内疗效。

Erlotinib-loaded albumin nanoparticles: A novel injectable form of erlotinib and its in vivo efficacy against pancreatic adenocarcinoma ASPC-1 and PANC-1 cell lines.

作者信息

Noorani M, Azarpira N, Karimian K, Heli H

机构信息

Department of Nanomedicine, School of Advanced Medical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran; Nanomedicine and Nanobiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Int J Pharm. 2017 Oct 5;531(1):299-305. doi: 10.1016/j.ijpharm.2017.08.102. Epub 2017 Aug 25.

Abstract

Erlotinib was loaded on albumin nanoparticles for the first time and the cytotoxic effect of the resulting nanoparticles against ASPC-1 and PANC-1 pancreatic adenocarcinoma cell lines was evaluated. The carrier (albumin nanoparticles, ANPs) was synthesized by desolvation method using a mixed solvent followed by thermal crosslinking for stabilization. ANPs and the drug-loaded ANPs were characterized by field emission scanning and transmission electron microscopies, particle size analysis and Fourier transform infrared spectroscopy. The nanoformulation had a size of <14nm with a good monodispersity. Drug loading and encapsulation efficiencies were evaluated as 27 and 44%. Cytotoxicity assays after 72h revealed the potential of ANPs to improve erlotinib toxicity (54% against 34% of free drug toward ASPC-1 cell line, and 52% against 30% toward PANC-1 cell line). Values of IC were obtained for both cell lines and indicated significant reduction in the erlotinib dose necessary for killing the cells, while, ANPs were completely safe. The results demonstrated that erlotinib-loaded ANPs had a remarkable potential for pancreatic cancer drug delivery.

摘要

厄洛替尼首次被负载于白蛋白纳米粒上,并评估了所得纳米粒对ASPC-1和PANC-1胰腺腺癌细胞系的细胞毒性作用。载体(白蛋白纳米粒,ANPs)采用混合溶剂的去溶剂化方法合成,随后进行热交联以实现稳定化。通过场发射扫描和透射电子显微镜、粒度分析以及傅里叶变换红外光谱对ANPs和载药ANPs进行了表征。该纳米制剂尺寸小于14nm,具有良好的单分散性。载药量和包封率分别评估为27%和44%。72小时后的细胞毒性试验显示,ANPs有提高厄洛替尼毒性的潜力(对ASPC-1细胞系,纳米粒组为54%,游离药物组为34%;对PANC-1细胞系,纳米粒组为52%,游离药物组为30%)。获得了两种细胞系的半数抑制浓度(IC)值,表明杀死细胞所需的厄洛替尼剂量显著降低,而ANPs完全安全。结果表明,载有厄洛替尼的ANPs在胰腺癌药物递送方面具有显著潜力。

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