This study aimed to develop a new colon-targeted drug delivery system via the preparation of ternary nanocomposite carriers based on organic polymer, aminoclay and lipid vesicles. Budesonide (Bud), an anti-inflammatory drug was chosen as a model drug and encapsulated into three different formulations: liposome (Bud-Lip), aminoclay-coated liposome (AC-Bud-Lip), and Eudragit® S100-aminoclay double coated liposome (EAC-Bud-Lip). The formation of the aminoclay-lipid vesicle nanocomposite was confirmed by energy dispersive X-ray spectrum, transmission electron microscopy, and Fourier-transform infrared spectroscopy. All formulations were produced with a high encapsulation efficiency in a narrow size distribution. Drug release from EAC-Bud-Lip was approximately 10% for 2-h incubation at pH 1.2, implying the minimal drug release in acidic gastric condition. At pH 7.4, EAC-Bud-Lip underwent significant size reduction and exhibited drug release profiles similar to that from AC-Bud-Lip, implying the pH-dependent removal of the outer coating layer. Compared to free Bud solution, EAC-Bud-Lip achieved a higher drug uptake in Caco-2 cells and exhibited a stronger inhibition of TNF-α and IL-6 secretion in LPS-stimulated Raw264.7 cells. Furthermore, a bio-distribution study in mice demonstrated that Eudragit® S100-aminoclay dual coating led to a higher colonic distribution with a longer residence time, which correlated well with the delayed systemic drug exposure in rats. Taken together, the present study suggests that the ternary nanocomposite carrier consisting of Eudragit® S100, aminoclay, and lipid vesicle might be useful as an effective colon-targeted drug delivery system.

中文翻译：

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基于有机粘土-脂质囊泡的三元纳米复合载体作为有效的结肠靶向药物递送系统：制备和体外/体内表征。


本研究旨在通过制备基于有机聚合物、氨基粘土和脂质囊泡的三元纳米复合载体，开发一种新型结肠靶向药物递送系统。选择抗炎药布地奈德（Bud）作为模型药物，封装成三种不同的制剂：脂质体（Bud-Lip）、氨基粘土包衣脂质体（AC-Bud-Lip）和Eudragit® S100-氨基粘土双层包衣脂质体（EAC-Bud-Lip）。通过能量色散X射线光谱、透射电子显微镜和傅里叶变换红外光谱证实了氨基粘土-脂质囊泡纳米复合材料的形成。所有配方均以窄尺寸分布且具有高封装效率。在 pH 1.2 下孵育 2 小时，EAC-Bud-Lip 的药物释放量约为 10%，这意味着在酸性胃条件下药物释放量最小。在 pH 7.4 时，EAC-Bud-Lip 的尺寸显着减小，并表现出与 AC-Bud-Lip 相似的药物释放曲线，这意味着外涂层的去除依赖于 pH 值。与游离的Bud溶液相比，EAC-Bud-Lip在Caco-2细胞中实现了更高的药物摄取，并且在LPS刺激的Raw264.7细胞中表现出更强的TNF-α和IL-6分泌抑制作用。此外，一项小鼠生物分布研究表明，Eudragit® S100-氨基粘土双重涂层可导致更高的结肠分布和更长的停留时间，这与大鼠体内延迟的全身药物暴露密切相关。综上所述，本研究表明，由 Eudragit® S100、氨基粘土和脂质囊泡组成的三元纳米复合载体可能可用作有效的结肠靶向药物递送系统。