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探讨槲皮素/阿司匹林载壳聚糖纳米粒包衣以 Eudragit L100 在治疗诱导的大鼠结直肠癌中的潜力。

Exploring the potential of quercetin/aspirin-loaded chitosan nanoparticles coated with Eudragit L100 in the treatment of induced-colorectal cancer in rats.

机构信息

Department of Pharmaceutics, College of Pharmacy, Jouf University, P.O. Box 2014, Sakaka, Saudi Arabia.

Department of Pharmacology, College of Pharmacy, Jouf University, P.O. Box 2014, Sakaka, Saudi Arabia.

出版信息

Drug Deliv Transl Res. 2023 Oct;13(10):2568-2588. doi: 10.1007/s13346-023-01338-3. Epub 2023 Mar 31.

Abstract

Growing evidence suggests quercetin and aspirin may have anticancer properties, notably in the case of colorectal cancer. The goal of this study was to create Pluronic F127 and polyethylene glycol4000 solid dispersion-loaded chitosan nanoparticles for colonic quercetin and aspirin delivery. In 1:1 polymeric stoichiometric ratio, solubility and complex formation were verified. Solid dispersion-loaded chitosan nanoparticles with a diameter of 244.45 ± 8.5 nm, a surface charge of 34.1 ± 3.3 mV, and encapsulation effectiveness of 76.3 ± 4.3% were generated under ideal conditions. In some cases, coating with Eudragit L100 resulted in a decrease in zeta potential and an increase in particle size. The coated formulation released the actives in a pH-dependent manner, considering their physicochemical features. Surprisingly, when compared to the actives' suspension and uncoated formulation, the coated formulation had greater anti-inflammatory efficacy, with a substantial reduction of PGE2 and IL-8 production in colonic tissues (16.9 ± 7.9 ng/g tissue and 134.9 ± 10.1 pg/g tissue, respectively). It also reversed most of the dimethyl hydrazine-induced histological alterations in the colon. It also demonstrated a greater reduction in TNF expression in colonic tissues. As a result, Eudragit L100-coated QT/AS-loaded chitosan nanoparticles are suggested to provide a potential platform for colonic delivery of quercetin and aspirin.

摘要

越来越多的证据表明槲皮素和阿司匹林可能具有抗癌特性,尤其是在结直肠癌的情况下。本研究的目的是制备载有壳聚糖纳米粒的 Pluronic F127 和聚乙二醇 4000 固体分散体,用于结肠部位的槲皮素和阿司匹林传递。在 1:1 的聚合化学计量比下,验证了溶解度和络合形成。在理想条件下,生成了直径为 244.45 ± 8.5nm、表面电荷为 34.1 ± 3.3mV、包封效率为 76.3 ± 4.3%的载药壳聚糖纳米粒。在某些情况下,用 Eudragit L100 进行包衣会导致 Zeta 电位降低和粒径增加。考虑到这些活性物质的物理化学特性,包衣制剂以 pH 依赖的方式释放活性物质。令人惊讶的是,与活性物质的混悬液和未包衣制剂相比,包衣制剂具有更强的抗炎效果,可显著降低结肠组织中 PGE2 和 IL-8 的产生(分别为 16.9 ± 7.9ng/g 组织和 134.9 ± 10.1pg/g 组织)。它还逆转了二甲肼诱导的结肠组织大部分组织学改变。它还显示出在结肠组织中 TNF 表达的更大减少。因此,建议用 Eudragit L100 包衣的 QT/AS 载药壳聚糖纳米粒为槲皮素和阿司匹林的结肠传递提供一个潜在的平台。

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