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载紫杉醇的脑胶质瘤细胞来源外泌体:两种加载技术的比较研究。

Paclitaxel incorporated exosomes derived from glioblastoma cells: comparative study of two loading techniques.

机构信息

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Department of Pharmaceutics, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

Daru. 2019 Dec;27(2):533-539. doi: 10.1007/s40199-019-00280-5. Epub 2019 Jul 17.

Abstract

BACKGROUND

Exosomes are natural nanoparticles that are involved in intercellular communication via transferring molecular information between cells. Recently, exosomes have been considered for exploitation as novel drug delivery systems due to their specific properties for carrying specific molecules and surface proteins.

METHODS

In this study, U-87 cell derived exosomes have been investigated for delivery of a potent chemotherapeutic agent, paclitaxel (PTX). Two methods of loading were utilized to incorporate PTX in exosomes and the exosomes pharmaceutical and cytotoxic characterizations were determined.

RESULTS

The drug loaded and empty exosomes were found to have particle size of 50-100 nm and zeta potential of ≈ - 20 mV. Loading capacity of 7.4 ng and 9.2 ng PTX into 1 μg of exosome total protein were also measured for incubation and sonication methods, respectively. Incorporation of PTX into exosomes significantly increased its cytotoxicity against U-87 cell line (59.92% cell viability) while it was found that the empty exosomes exhibited cell viability of 91.98%.

CONCLUSIONS

Loading method could affect the loading capacity of exosomes and their encapsulated chemotherapeutic molecule showed higher cytotoxicity into exosomes. These results promise exosomes as appropriate drug delivery system for glioblastoma multiform (GBM) treatment.

摘要

背景

外泌体是一种天然的纳米颗粒,通过在细胞间传递分子信息参与细胞间通讯。最近,由于其携带特定分子和表面蛋白的特定特性,外泌体被认为是新型药物传递系统的潜在用途。

方法

本研究考察了 U-87 细胞衍生的外泌体作为一种有效的化疗药物紫杉醇(PTX)的传递系统。利用两种载药方法将 PTX 载入外泌体,并对载药外泌体的药学和细胞毒性特征进行了测定。

结果

负载药物和空载外泌体的粒径为 50-100nm,ζ电位约为-20mV。孵育法和超声法的载药能力分别为每 1μg 外泌体总蛋白 7.4ng 和 9.2ng 的 PTX。将 PTX 载入外泌体显著提高了其对 U-87 细胞系的细胞毒性(细胞活力 59.92%),而空载外泌体的细胞活力为 91.98%。

结论

载药方法可能会影响外泌体的载药能力,其包裹的化疗药物分子在进入外泌体后显示出更高的细胞毒性。这些结果预示着外泌体可能成为治疗多形性胶质母细胞瘤(GBM)的合适药物传递系统。

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Physical exosome:exosome interactions.物理外泌体:外泌体相互作用。
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Milk-derived exosomes for oral delivery of paclitaxel.牛奶来源的外泌体用于紫杉醇的口服递送。
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Exosomes as novel bio-carriers for gene and drug delivery.外泌体作为用于基因和药物递送的新型生物载体。
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