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壳聚糖基聚合物纳米粒的制备及特性研究——用于结直肠癌靶向治疗的伊马替尼。

Fabrication and characterization of chitosan-based polymeric nanoparticles of Imatinib for colorectal cancer targeting application.

机构信息

Department of Pharmaceutics, ISF College of Pharmacy, Moga 142001, Punjab, India; Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, Uttar Pradesh, India.

出版信息

Int J Biol Macromol. 2020 May 15;151:104-115. doi: 10.1016/j.ijbiomac.2020.02.151. Epub 2020 Feb 15.

Abstract

The main objective of this research was to develop chitosan based polymeric nanoparticles of Imatinib (IMT-PNPs) for colorectal cancer targeting. The ionic gelation technique and central composite design was implemented to prepare IMT-PNPs. Out of 21 batches, F10 formulation was found to be optimized. The F10 was further evaluated for surface morphology, in-vitro drug release and release kinetic study, in-vitro drug deposition study, histopathological study, colon tissue uptake study using fluorescence microscopy, in-vitro cytotoxicity study & stability studies. The optimized formulations were found to have 208 ± 0.01 nm particle size, -32.56 ± 0.03 mV of zeta potential, 86.45 ± 0.05% in-vitro cumulative drug release & 68.52 ± 0.01% drug entrapment efficacy. Florescence study indicates epithelial colon cells parade higher fluorescent nanoparticle accumulation after i.v. administration. The IMT-PNPs formulations show only 0.46% hemolysis, which indicates the formulation is safer for i.v. administration. In histopathological evaluation, the final formulations show no sign of damage in tissues, which indicates the final formulation can be safely administered through i.v. route. From the MTT assay, it can be witnessed that encapsulated IMT-PNPs produces higher & controlled cytotoxicity in CT26 colon carcinoma cell lines. The outcomes of this research confined, IMT-PNPs could be an effective approach in colorectal cancer targeting using i.v. route.

摘要

本研究的主要目的是开发基于壳聚糖的伊马替尼(IMT-PNPs)聚合物纳米粒用于结直肠癌靶向。采用离子凝胶技术和中心复合设计来制备 IMT-PNPs。在 21 批中,发现 F10 制剂是优化的。进一步评估 F10 的表面形态、体外药物释放和释放动力学研究、体外药物沉积研究、荧光显微镜下的组织病理学研究、结肠组织摄取研究、体外细胞毒性研究和稳定性研究。优化的制剂具有 208 ± 0.01nm 的粒径、-32.56 ± 0.03mV 的 zeta 电位、86.45 ± 0.05%的体外累积药物释放和 68.52 ± 0.01%的药物包封效率。荧光研究表明,静脉给药后上皮结肠细胞显示出更高的荧光纳米颗粒积累。IMT-PNPs 制剂的溶血率仅为 0.46%,表明该制剂更适合静脉给药。在组织病理学评价中,最终制剂在组织中没有显示出任何损伤的迹象,表明最终制剂可以通过静脉途径安全给药。从 MTT 测定可以看出,包封的 IMT-PNPs 在 CT26 结肠癌细胞系中产生更高和更可控的细胞毒性。本研究的结果表明,IMT-PNPs 可能是通过静脉途径靶向结直肠癌的有效方法。

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