Purpose

To design pH switchable LLC (lyotropic liquid crystal) nanoparticles with the goal of exclusively delivering 5-Fluorouracil (5-FU) in the colonic region of GIT for the treatment of colon cancer.

Methods

The proportions of monoolein (MO), oleic acid (OA), and pluronic F127 were chosen using the quadratic model of D-optimal mixture design for LLC nanoparticle batches. The formulations were characterized and evaluated for (i) adhesion work at porcine stomach, (ii) adhesion work at porcine large intestine, (iii) drug release up to pH 6.8, and (iv) drug release at pH 7.4. The models developed during data analysis were optimized and subjected to pharmacokinetic and in vivo scintigraphic study.

Results

The design proposed three optimal formulations OLN1, OLN2, and OLN3, where OLN3 outperformed the rest in terms of 5-FU release profile as well as comparable work of adhesion at porcine stomach and large intestine. The gamma scintigraphic images and pharmacokinetic results of OLN3 with 30% MO, 62.565% OA, and 7.435% pluronic F127 indicated that the hexagonal configuration of the system prevented 5-FU absorption from the upper GIT and no substantial release of the drug occurred within 6-h period. However, there was considerable release from the system due to hexagonal structure converting to cubic structure at colonic pH.

Conclusions

Upon oral administration, OLN3 preserved its integrity during its passage through stomach, successfully entered, and was evenly spread in the colon during the 12-h study period demonstrating the required properties in terms of drug targeting.

中文翻译：

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靶向结肠的 pH 可切换 LLC 纳米颗粒：使用 D 优化设计进行优化

目的

设计 pH 可切换 LLC（溶致液晶）纳米颗粒，目标是在 GIT 的结肠区域专门提供 5-氟尿嘧啶 (5-FU) 用于治疗结肠癌。

方法

使用 LLC 纳米颗粒批次的 D 最佳混合物设计的二次模型选择单油精 (MO)、油酸 (OA) 和普朗尼克 F127 的比例。对制剂进行表征和评估：(i) 在猪胃中的粘附作用，(ii) 在猪大肠中的粘附作用，(iii) 药物释放至 pH 6.8，和 (iv) 药物释放在 pH 7.4。在数据分析过程中开发的模型经过优化，并进行了药代动力学和体内闪烁显像研究。

结果

该设计提出了三种最佳配方 OLN1、OLN2 和 OLN3，其中 OLN3 在 5-FU 释放曲线以及在猪胃和大肠的可比粘附工作方面优于其他配方。具有 30% MO、62.565% OA 和 7.435% Pluronic F127 的 OLN3 的 γ 闪烁显像图像和药代动力学结果表明，该系统的六边形结构阻止了 5-FU 从上 GIT 吸收，并且在 6 天内没有发生药物的大量释放。 -h 期间。然而，由于在结肠 pH 下六边形结构转变为立方结构，系统中有相当多的释放。

结论

口服给药后，OLN3 在通过胃的过程中保持其完整性，成功进入，并在 12 小时的研究期间均匀分布在结肠中，证明了药物靶向所需的特性。