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Biodistribution, Safety and Organ Toxicity of Docetaxel-Loaded in HER-2 Aptamer Conjugated Ecoflex® Nanoparticles in a Mouse Xenograft Model of Ovarian Cancer.
Recent Patents on Nanotechnology ( IF 2.0 ) Pub Date : 2018-11-30 , DOI: 10.2174/1872210513666181128162403
Erfaneh Ghassami 1 , Jaleh Varshosaz 1 , Mohsen Minaiyan 2 , Mehrab Nasirikenari 3 , Seyed M Hoseini 4
Affiliation  

BACKGROUND Docetaxel is a notably efficient anticancer drug administered for several types of malignancies including ovarian cancer. However, various side effects caused either by the nonspecific distribution of the active ingredient or by high contents of Tween 80 and ethanol in the currently marketed formulations, could even deprive the patients of the treatment. OBJECTIVES In the current study, a novel targeted delivery system composed of Ecoflex® polymeric nanoparticles loaded with docetaxel and equipped with HER-2 specific aptamer molecules was evaluated regarding blood and tissue toxicity, and biodistribution. METHOD The tumor-bearing nude mice, achieved by subcutaneous injection of SKOV-3 cells, were divided into four groups treated with normal saline, Taxotere®, targeted docetaxel nanoparticles, and non-targeted docetaxel nanoparticles. Few patents were alos cied in the article. RESULTS According to the results of hematologic evaluations, almost all hematologic parameters were in normal range with no significant difference among the four groups. Histopathological studies revealed that treatment with targeted nanoparticles caused a remarkable reduction in mitosis in tumor sections and overall reduced organ toxicity compared with Taxotere®. The only exception was spleen in which more damage was caused by the nanoparticles. The results of the biodistribution study were also in accordance with pathological assessments, with significantly lower drug concentration in non-tumor tissues, except for spleen, when targeted nanoparticles were used compared with Taxotere®. CONCLUSION These results could evidence the efficiency of the targeted delivery system in concentrating the drug cargo mostly in its site of action leading to the elimination of its adverse effects caused by exposure of other tissues to the cytotoxic agent.

中文翻译:

在卵巢癌小鼠异种移植模型中,HER-2适体缀合的Ecoflex®纳米颗粒中负载多西他赛的生物分布,安全性和器官毒性。

背景技术多西紫杉醇是用于包括卵巢癌在内的几种类型的恶性肿瘤的显着有效的抗癌药。但是,由于活性成分的非特异性分布或目前市场上销售的配方中吐温80和乙醇的含量较高而引起的各种副作用甚至可能使患者失去治疗能力。目的在当前研究中,针对血液和组织毒性以及生物分布,评估了一种新型的靶向递送系统,该系统由装载多西紫杉醇并配有HER-2特异性适体分子的Ecoflex®聚合物纳米颗粒组成。方法通过皮下注射SKOV-3细胞获得的荷瘤裸鼠分为四组,分别用生理盐水,Taxotere®,靶向多西他赛纳米颗粒和非靶向多西他赛纳米颗粒治疗。文章中几乎没有专利被取消。结果根据血液学评估结果,几乎所有血液学参数均在正常范围内,四组之间无显着差异。组织病理学研究表明,与Taxotere®相比,靶向纳米颗粒治疗可显着减少肿瘤切片中的有丝分裂,并全面降低器官毒性。唯一的例外是脾脏,其中纳米颗粒造成了更多的损害。生物分布研究的结果也符合病理评估,与Taxotere®相比,使用脾脏靶向纳米粒子时,除脾脏外,非肿瘤组织中的药物浓度明显降低。
更新日期:2019-11-01
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