SN38和雷帕霉素白蛋白结合纳米颗粒共同递送抗乳腺癌。

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Sanaz Jamshidfar, Marzieh Ebrahimi, Reyhaneh Varshochian, Navid Goodarzi, Javad Firouzi, Mahsa Rezaei, Seyed Nasser Ostad, Yalda Hosseinzadeh Ardakani, Rassoul Dinarvand
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引用次数: 0

摘要

背景:在单个纳米颗粒平台内共同递送两种治疗剂提供了一种潜在的策略,可以提高治疗效果,同时最大限度地减少不良反应。白蛋白作为一种生物相容性载体,可以通过增强渗透性和滞留性(EPR)获得被动靶向,从而促进货物同时递送到肿瘤区域。目的:本研究旨在开发、表征和评估一种结合雷帕霉素和SN38的双药递送系统,利用纳米颗粒白蛋白结合技术,用于治疗乳腺癌。方法:采用探针超声法制备SN38和雷帕霉素白蛋白结合NPs。利用动态光散射(DLS)和场发射扫描电镜(FESEM)技术对NPs进行了表征,确定了NPs的水动力直径和结构性质。采用经验证的反相高效液相色谱(RP-HPLC)方法测定药物的载药量(DL)和包封效率(EE)。进行细胞毒性试验、细胞内化试验、定量细胞摄取试验、菌落形成试验和球体形成试验。为了在生物分布部分追踪NPs的命运,我们将NPs静脉注射到BALB/c荷瘤小鼠中。结果:空白NPs流体动力学直径约为121 nm,药物掺入形成的NPs尺寸约为200 nm。MTT法对空白白蛋白NPs无毒性反应。载药NPs的MTT试验显示,与单载药NPs相比,双载药NPs的毒性更高。共聚焦图像和流式细胞术显示NPs在4T1细胞细胞质间隙大量积聚。与对照组相比,各试验组的菌落形成和球形形成均显著减少。NPs由于其合适的大小,在体内也优先在肿瘤区域积累。结论:所设计的给药系统在乳腺癌治疗中具有很大的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Co-delivery of SN38 and rapamycin albumin bound nanoparticles against breast Cancer.

Background: The co-delivery of two therapeutic agents within a single nanoparticle platform offers a potential strategy to improve treatment efficacy while minimizing adverse effects. Albumin as a biocompatible carrier could facilitate simultaneous delivery of cargos to the tumoral region based on passive targeting gained by enhanced permeability and retention (EPR).

Objectives: This study aimed to develop, characterize, and assess a dual-drug delivery system incorporating rapamycin and SN38, utilizing the nanoparticle albumin bound technique, for the treatment of breast cancer.

Methods: Albumin bound NPs of SN38 and rapamycin were prepared using probe sonication method. NPs were characterized using dynamic light scattering (DLS) and field emission scanning electron microscopy (FESEM) techniques to confirm their hydrodynamic diameter and structural properties. Drug loading (DL) and entrapment efficiency (EE) were measured using validated reverse phase high performance liquid chromatography (RP-HPLC) methods. Cellular cytotoxicity assay, cellular internalization, quantitatively cellular uptake, colony formation assay, and sphere formation assay were performed. To track NPs destiny as a 24 h follow up in the biodistribution part, NPs were intravenously injected to the BALB/c tumor bearing mice.

Results: Blank NPs showed hydrodynamic diameter of about 121 nm, drug incorporation resulted in sizes around 200 nm. No toxicity was observed by MTT assay for blank albumin NPs. MTT assay of drug loaded NPs showed higher toxicity for dual drug loaded NPs compared to single drug loaded NPs. Confocal images and flow cytometry showed high accumulation of NPs in cytoplasmic space of 4T1 cells. All of the experimental groups showed significant decrease in colony formation and sphere formation in comparison to the control group. NPs were also preferentially accumulated in the tumoral region in vivo due to their suitable size.

Conclusion: In conclusion, the designed drug delivery system proposes great potential for breast cancer treatment.

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来源期刊
DARU Journal of Pharmaceutical Sciences
DARU Journal of Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-
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期刊介绍: DARU Journal of Pharmaceutical Sciences is a peer-reviewed journal published on behalf of Tehran University of Medical Sciences. The journal encompasses all fields of the pharmaceutical sciences and presents timely research on all areas of drug conception, design, manufacture, classification and assessment. The term DARU is derived from the Persian name meaning drug or medicine. This journal is a unique platform to improve the knowledge of researchers and scientists by publishing novel articles including basic and clinical investigations from members of the global scientific community in the forms of original articles, systematic or narrative reviews, meta-analyses, letters, and short communications.
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