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壳聚糖/PLA/5-FU/g-C3N4-DOX/g-C3N4-PTX 三轴纳米纤维的同步控释用于体外乳腺癌治疗。

Simultaneous controlled release of 5-FU, DOX and PTX from chitosan/PLA/5-FU/g-C3N4-DOX/g-C3N4-PTX triaxial nanofibers for breast cancer treatment in vitro.

机构信息

Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Faculty of Chemical Engineering, Noshirvani University, Babol, Iran.

出版信息

Colloids Surf B Biointerfaces. 2019 Jul 1;179:495-504. doi: 10.1016/j.colsurfb.2019.04.026. Epub 2019 Apr 13.

DOI:10.1016/j.colsurfb.2019.04.026
PMID:31005745
Abstract

In the present study, the tri-layer nanofibers were synthesized via triaxial electrospinning process to control the sustained delivery of Doxorubicin (DOX), Paclitaxel (PTX) and 5- fluorouracil (5-FU) anticancer drugs from nanofibers. The 5-FU molecules were incorporated into the core solution (chitosan/polyvinyl alcohol (CS/PVA)) to fabricate the CS/PVA/5-FU inner layer of nanofibers. The intermediate layer was prepared from poly(lactic acid)/chitosan (PLA/CS) nanofibers. The DOX and PTX molecules were initially loaded into the g-C3N4 nanosheets and following were incorporated into the PLA/CS solution to fabricate the outer layer of nanofibers. The synthesized nanosheets and nanofibers were characterized using XRD, SEM, TEM and UV-vis analysis. The PLA/PVA/CS/FU/g-C3N4/DOX/PTX single layer nanofibers were also synthesized via electrospinning method. The drug loading efficiency, degradation rate and anticancer drugs release profiles from single layer and tri-layer nanofibers were investigated under various intermediate and shell layer thicknesses. The pharmacokinetic studies were performed to understand the drugs release mechanism from nanofibers. The cell viability and cell attachment of drug loaded single layer and tri-layer nanofibers toward the MCF-7 breast cancer cells were examined to achieve an optimum nanofibrous formulation for the breast cancer treatment. The obtained results revealed the high activity of tri-layer nanofibers for the breast cancer cells killing.

摘要

在本研究中,通过三轴静电纺丝工艺合成了三层纳米纤维,以控制多柔比星(DOX)、紫杉醇(PTX)和 5-氟尿嘧啶(5-FU)抗癌药物从纳米纤维中的持续释放。5-FU 分子被掺入芯溶液(壳聚糖/聚乙烯醇(CS/PVA))中,以制备 CS/PVA/5-FU 内层纳米纤维。中间层由聚乳酸/壳聚糖(PLA/CS)纳米纤维制成。DOX 和 PTX 分子最初被加载到 g-C3N4 纳米片中,然后被掺入 PLA/CS 溶液中,以制备纳米纤维的外层。通过 XRD、SEM、TEM 和 UV-vis 分析对合成的纳米片和纳米纤维进行了表征。还通过静电纺丝法合成了 PLA/PVA/CS/FU/g-C3N4/DOX/PTX 单层纳米纤维。研究了不同中间层和壳层层厚度下,单层和三层纳米纤维的药物负载效率、降解率和抗癌药物释放曲线。进行了药代动力学研究以了解纳米纤维中药物释放的机制。研究了载药单层和三层纳米纤维对 MCF-7 乳腺癌细胞的细胞活力和细胞附着,以获得用于乳腺癌治疗的最佳纳米纤维配方。结果表明,三层纳米纤维对乳腺癌细胞具有很高的杀伤活性。

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