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含植酸和麻疯树凝集素的果胶包裹金纳米复合材料:1,2-二甲基肼诱导 Wistar 大鼠结肠癌发生,PI3K/Akt、COX-2 和血清代谢组学作为潜在靶点。

Pectin-encrusted gold nanocomposites containing phytic acid and jacalin: 1,2-dimethylhydrazine-induced colon carcinogenesis in Wistar rats, PI3K/Akt, COX-2, and serum metabolomics as potential targets.

机构信息

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University (BBAU), A Central University, Vidya Vihar, Raebareli Road, Lucknow, UP, 226025, India.

Centre of Biomedical Research (CBMR), Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) Campus, Raebareli Road, Lucknow, UP, 226014, India.

出版信息

Drug Deliv Transl Res. 2019 Feb;9(1):53-65. doi: 10.1007/s13346-018-00605-y.

Abstract

Phytic acid (PA) has momentous chemotherapeutic potential. Due to the chelate formation and rapid elimination, it is not popular in cancer treatment. The present work was inquested to develop a surface-modified nanoformulation of PA which prevents its speedy elimination and maximizes chemotherapeutic action. Chloroauric acid was reduced with pectin to produce pectin-gold nanoparticles (PGNPs). PGNPs were incubated with PA and jacalin for drug loading and surface modifications, respectively, to form PA-loaded jacalin-pectin-gold nanoparticles (PA-J-PGNPs). Formulation(s) were assessed for various pharmaceutical/pharmacological parameters. To validate the efficacy against colon carcinogenesis, formulation(s) were assessed in 1,2-dimethylhydrazine (DMH)-treated Wistar rats. DMH treatment distorted colonic architecture, oxidative, and hemodynamic parameters, which were favorably restored by PA-J-PGNP administration. To further confirm our deliberations, formulation(s) were also examined against DMH-altered metabolic changes and expression of markers pertaining to cellular proliferation, which was reinstated by PA-J-PGNPs. Our findings establish PA formulation(s) as a promising approach for suppression of colon carcinogenesis.

摘要

植酸(PA)具有重要的化疗潜力。由于螯合形成和快速消除,它在癌症治疗中并不流行。本工作旨在开发一种表面修饰的 PA 纳米制剂,以防止其快速消除并最大限度地发挥化疗作用。氯金酸与果胶还原生成果胶-金纳米颗粒(PGNPs)。PGNPs 分别与 PA 和 jacalin 孵育以进行药物负载和表面修饰,以形成负载 PA 的 jacalin-pectin-gold 纳米颗粒(PA-J-PGNPs)。制剂的各种药物/药理学参数进行评估。为了验证其对结肠癌发生的疗效,在 1,2-二甲基肼(DMH)处理的 Wistar 大鼠中评估了制剂。DMH 处理破坏了结肠的结构、氧化和血液动力学参数,而 PA-J-PGNP 的给药则有利于这些参数的恢复。为了进一步证实我们的讨论,还检查了制剂对 DMH 改变的代谢变化和与细胞增殖相关标志物的表达的影响,而 PA-J-PGNPs 则恢复了这些变化和标志物的表达。我们的研究结果表明,PA 制剂是抑制结肠癌发生的一种有前途的方法。

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