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载有卡培他滨的马铃薯淀粉-壳聚糖纳米粒:一种用于侵袭性结肠癌的靶向治疗和改善预后的新方法。

Capecitabine loaded potato starch-chitosan nanoparticles: A novel approach for targeted therapy and improved outcomes in aggressive colon cancer.

机构信息

Department of Pharmaceutics, School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra 425405, India.

Department of Pharmaceutics, School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra 425405, India.

出版信息

Eur J Pharm Biopharm. 2024 Jul;200:114328. doi: 10.1016/j.ejpb.2024.114328. Epub 2024 May 17.

Abstract

Aggressive colon cancer treatment poses significant challenges. This study investigates the potential of innovative carbohydrate-based nanoparticles for targeted Capecitabine (CTB) delivery. CTB nanoparticles were synthesized by conjugating CTB with potato starch and chitosan using ultrasonication, hydrolysis, and ionotropic gelation. Characterization included drug loading, rheology, Surface-Enhanced Raman Spectroscopy (SERS), Fourier-Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and Thermogravimetric Analysis (TGA). In vitro and in vivo antitumor activity was evaluated using HT-29 cells and N, N-dimethylhydrazine-induced Balb/c mice, respectively. Cellular assays assessed angiogenesis, migration, proliferation, and apoptosis. Nanoparticles exhibited a mean size of 245 nm, positive zeta potential (+30 mV), high loading efficacy (76 %), and sustained drug release (92 % over 100 h). CTB-loaded nanoparticles displayed superior colon histology, reduced tumour scores, and inhibited VEGD and CD31 expression compared to free CTB. Cellular assays confirmed significant antitumor effects, including reduced tube formation, migration, and proliferation, and increased apoptosis. This study demonstrates the promise of CTB-loaded potato starch-chitosan nanoparticles for aggressive colon cancer treatment. These findings highlight the potential of these nanoparticles for further evaluation in diverse cancer models.

摘要

激进型结肠癌的治疗极具挑战性。本研究旨在探讨基于创新碳水化合物的纳米颗粒在卡培他滨(CTB)靶向递送上的潜力。通过超声处理、水解和离子凝胶化,将 CTB 与马铃薯淀粉和壳聚糖偶联,合成 CTB 纳米颗粒。对药物载量、流变学、表面增强拉曼光谱(SERS)、傅里叶变换红外光谱(FTIR)、差示扫描量热法(DSC)、X 射线衍射(XRD)和热重分析(TGA)进行了表征。分别采用 HT-29 细胞和 N, N-二甲基肼诱导的 Balb/c 小鼠评估了体外和体内的抗肿瘤活性。细胞分析评估了血管生成、迁移、增殖和凋亡。纳米颗粒的平均粒径为 245nm,具有正 zeta 电位(+30mV)、高载药效率(76%)和持续的药物释放(100 小时内释放 92%)。与游离 CTB 相比,载 CTB 的纳米颗粒表现出更好的结肠组织学特性,降低了肿瘤评分,并抑制了 VEGD 和 CD31 的表达。细胞分析证实了其显著的抗肿瘤作用,包括减少管形成、迁移和增殖,以及增加凋亡。本研究表明,载 CTB 的马铃薯淀粉-壳聚糖纳米颗粒有望用于激进型结肠癌的治疗。这些发现突出了这些纳米颗粒在不同癌症模型中进一步评估的潜力。

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