影响通过肠道淋巴途径与乙醇酸表面偶联的纳米颗粒口服生物利用度的选定因素,Molecular Pharmaceutics

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影响通过肠道淋巴途径与乙醇酸表面偶联的纳米颗粒口服生物利用度的选定因素
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2020-10-16 , DOI: 10.1021/acs.molpharmaceut.0c00764
Kyoung Sub Kim ₁ , Kenichi Suzuki _{1,

2} , Hana Cho ₁ , You Han Bae ₁

Affiliation

在这里，我们描述了表面用胆汁酸修饰的纳米颗粒的吸收途径，并介绍了影响胃肠道 (GIT) 口服生物利用度 (BA) 的环境因素。该方法利用与甘胆酸 (G/CPN) 共轭的 100 nm 荧光标记的羧化聚苯乙烯纳米粒子 (CPN) 来排除潜在的伪影（如果存在）以及评估 GIT 中 G/CPN 转运和测量 BA 的不稳定性问题. 在体外使用表达顶端胆汁酸钠转运蛋白的 SK-BR-3 的研究表明，一旦 G/CPN 被内化，它在细胞中的停留时间是 CPN 的 2.9 倍，间接表明 G/CPN 在 SK 中采用不同于 CPN 的细胞内运输途径-BR-3 细胞。在 Caco-2 细胞单层中，G/CPN 在不破坏紧密连接的情况下穿过单层。G/CPN 在啮齿动物中口服给药时，在 GIT 中显示出持续的转运时间至少 4 小时，并被吸收到肠道淋巴系统中并循环到血液中。口服给药前后摄入食物会延迟 G/CPN 吸收并降低 BA。麻醉条件下胃肠动力的降低使 G/CPN 的相对 BA 增加了 74%。因此，

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Selected Factors Affecting Oral Bioavailability of Nanoparticles Surface-Conjugated with Glycocholic Acid via Intestinal Lymphatic Pathway

Here, we describe the absorption pathways of nanoparticles whose surface is modified with bile acid and present environmental factors that influence oral bioavailability (BA) from the gastrointestinal tract (GIT). The approach utilized 100 nm sized fluorescence-labeled, carboxylated polystyrene nanoparticles (CPN) conjugated with glycocholic acid (G/CPN) to exclude potential artifacts, if existing, and instability issues in evaluating the transit of G/CPN in the GIT and measuring BA. The in vitro study using SK-BR-3 that expresses the apical sodium bile acid transporter showed that once G/CPN is internalized, it stayed 2.9 times longer in the cells than CPN, indirectly suggesting that G/CPN takes intracellular trafficking pathways different from CPN in SK-BR-3 cells. In a Caco-2 cell monolayer, G/CPN passed through the monolayer without damaging the tight junction. G/CPN, when administered orally in rodents, showed sustained transit time in the GIT for at least 4 h and was absorbed into the intestinal lymphatic system and circulated into the blood. Ingestion of food before and after oral administration delays G/CPN absorption and decreases BA. A decrease in gastrointestinal motility by anesthetic condition increased the relative BA of G/CPN by up to 74%. Thus, the oral BA of G/CPN can be optimized by taking food ingestion and gastrointestinal motility into account.

更新日期：2020-11-02

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