Chitosan nanoparticles of imatinib mesylate coated with TPGS for the treatment of colon cancer: In-vivo & in-vitro studies

IF 10.7 1区化学 Q1 CHEMISTRY, APPLIED

Carbohydrate Polymers Pub Date : 2024-11-04 DOI:10.1016/j.carbpol.2024.122935

Darshan Bhirud , Sankha Bhattacharya , Harshvardhan Raval , Preeti Chidambar Sangave , Girdhari Lal Gupta , Gaurav Paraskar , Megha Jha , Satyam Sharma , Sateesh Belemkar , Devendra Kumar , Rahul Maheshwari , Mayank Sharma

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Abstract

The study aimed to develop and evaluate chitosan-based nanoparticles coated with TPGS for the targeted delivery of imatinib mesylate to colon cancer cells. Particle size and zeta potential analysis were within the acceptable range for targeting colon cancer. CS-IMT-TPGS-NPs had a significant positive zeta potential of 30.4 mV, suggesting improved cellular intake. FE-SEM and TEM demonstrated that the nanoparticles appeared spherical, smooth, and did not aggregate, with a visible TPGS coating. XRD confirmed that crystalline imatinib transitioned to an amorphous state during nano formulation. In-vitro tests on HCT-116 cells demonstrated that CS-IMT-TPGS-NPs outperformed free IMT regarding cytotoxicity, apoptosis induction, cellular uptake, and cell migration inhibition. Additionally, the nanoparticles were examined in vitro using mitochondrial membrane potential, DNA fragmentation, GAPDH relative gene expression, ROS estimation, and cell cycle analysis. The effect of therapy on expected colon-associated bacterial strains was also investigated. The biocompatibility of nanoparticles was assessed by hemolysis and platelet aggregation experiments. The anti-inflammatory impact was determined using the HET-CAM test. Non-Fickian diffusion at pH 5.5 resulted in sustained in-vitro drug release, with no initial burst. In-vivo investigations using albino Wistar rats suggest pharmacokinetic properties for produced nanoparticles, whereas histopathological examinations assess acute toxicity.

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涂有 TPGS 的甲磺酸伊马替尼壳聚糖纳米粒子用于治疗结肠癌：体内和体外研究

该研究旨在开发和评估涂有 TPGS 的壳聚糖基纳米粒子，用于向结肠癌细胞靶向递送甲磺酸伊马替尼。粒度和 zeta 电位分析均在结肠癌靶向可接受的范围内。CS-IMT-TPGS-NPs 的 zeta 电位显著为正 30.4 mV，表明细胞摄取量有所提高。FE-SEM 和 TEM 显示，纳米颗粒呈球形、光滑、不聚集，并有可见的 TPGS 涂层。XRD 证实，结晶伊马替尼在纳米制剂过程中转变为无定形状态。对 HCT-116 细胞进行的体外测试表明，CS-IMT-TPGS-NPs 在细胞毒性、凋亡诱导、细胞摄取和细胞迁移抑制方面优于游离 IMT。此外，还使用线粒体膜电位、DNA 断裂、GAPDH 相对基因表达、ROS 估计和细胞周期分析对纳米粒子进行了体外检测。此外，还研究了治疗对预期结肠相关细菌菌株的影响。通过溶血和血小板聚集实验评估了纳米颗粒的生物相容性。使用 HET-CAM 试验确定了抗炎效果。在 pH 值为 5.5 的条件下，非费克式扩散导致体外药物持续释放，且无初始猝灭。利用白化 Wistar 大鼠进行的体内研究表明，所生产的纳米粒子具有药代动力学特性，而组织病理学检查则评估了其急性毒性。

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来源期刊

Carbohydrate Polymers 化学-高分子科学

CiteScore

22.40

自引率

8.00%

发文量

1286

审稿时长

47 days

期刊介绍： Carbohydrate Polymers stands as a prominent journal in the glycoscience field, dedicated to exploring and harnessing the potential of polysaccharides with applications spanning bioenergy, bioplastics, biomaterials, biorefining, chemistry, drug delivery, food, health, nanotechnology, packaging, paper, pharmaceuticals, medicine, oil recovery, textiles, tissue engineering, wood, and various aspects of glycoscience. The journal emphasizes the central role of well-characterized carbohydrate polymers, highlighting their significance as the primary focus rather than a peripheral topic. Each paper must prominently feature at least one named carbohydrate polymer, evident in both citation and title, with a commitment to innovative research that advances scientific knowledge.