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天冬氨酸标记的碳纳米管作为一种向乳腺癌细胞递送多西紫杉醇的工具:降低了细胞毒性,同时提高了细胞毒性。

Aspartic acid tagged carbon nanotubols as a tool to deliver docetaxel to breast cancer cells: Reduced hemotoxicity with improved cytotoxicity.

机构信息

Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Dist. Ajmer, Rajasthan 305 817, India.

Department of Pharmacy, Birla Institute of Technology and Science-Pilani (BITS), Pilani Campus, Vidya Vihar, Pilani, Rajasthan 333 031, India.

出版信息

Toxicol In Vitro. 2019 Sep;59:126-134. doi: 10.1016/j.tiv.2019.04.012. Epub 2019 Apr 13.

Abstract

The present study aimed to explore the potential of hydroxylated carbon nanotubes (CNTnols) conjugated with aspartic acid for the delivery of docetaxel (DTX) to breast cancer cells. The conjugate was well-characterized by FT-IR, NMR, XRD and FE-SEM. The nanoconjugate offered a hydrodynamic diameter of 86.31 ± 1.02 nm, with a PDI of 0.113 and zeta potential of -41.6 ± 0.17 mV. The designed nanosystem offered a controlled & pH dependent release vouching release of drug in the cancerous cytosol, not in blood, assuring delivery of the pay-load to the site of action. The carriers offered substantial hemocompatibility and lower plasma protein binding, ensuring more drug available at the site of action. The in-vitro cell viability studies in MDA MB-231 cells inferred approx. 2.8 times enhancement in the cytotoxicity potential of the conjugate vis-à-vis plain drug. Pharmacokinetic studies also corroborated the superiority of the designed nanoconjugate in terms of enhanced bioavailable fractions, reduced clearance and longer bioresidence to that of plain docetaxel. The present studies, successfully provide a workable nanomedicine, loaded with a BCS class-IV drug, for improved efficacy and safety in breast cancer.

摘要

本研究旨在探索经天冬氨酸修饰的羟基化碳纳米管(CNTnols)用于递送达托昔康(DTX)至乳腺癌细胞的潜力。该缀合物通过傅里叶变换红外光谱(FT-IR)、核磁共振(NMR)、X 射线衍射(XRD)和场发射扫描电子显微镜(FE-SEM)进行了很好的表征。纳米复合物的水动力直径为 86.31±1.02nm,PDI 为 0.113,zeta 电位为-41.6±0.17mV。该设计的纳米系统提供了一种控制和 pH 依赖性释放,保证药物在癌细胞溶酶体中释放,而不在血液中释放,从而确保有效载荷递送到作用部位。载体具有显著的血液相容性和较低的血浆蛋白结合率,确保在作用部位有更多的药物可用。在 MDA MB-231 细胞中的体外细胞活力研究表明,与普通药物相比,该缀合物的细胞毒性潜力增强了约 2.8 倍。药代动力学研究也证实了设计的纳米复合物在增强生物利用度分数、降低清除率和延长生物滞留时间方面优于普通多西紫杉醇。本研究成功地提供了一种可行的载有 BCS 类-IV 药物的纳米药物,以提高乳腺癌的疗效和安全性。

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