Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, Universidad de Santiago de Compostela, Spain.
Departamento de Microbiología y Parasitología, Instituto de Investigación y Análisis Alimentarios, Universidad de Santiago de Compostela, Spain.
Int J Pharm. 2017 Feb 25;518(1-2):86-104. doi: 10.1016/j.ijpharm.2016.12.057. Epub 2016 Dec 28.
This research addresses the development and in vitro evaluation of a microparticulate system intended for intestine-targeted delivery of curcumin (CRM), a natural polyphenol with anti-inflammatory properties. Microspheres (Ms) based on zein (ZN) and Gantrez AN119 (PVMMA) were prepared by spray-drying and coated with a pH-sensitive polymer (Eudragit FS30D). An experimental design was performed to optimize the microparticulate formulation. A detailed characterization of systems was carried out by SEM, DSC, FTIR, particle size, ζ potential measurements and in vitro CRM release. The optimized formulation was evaluated in LPS-stimulated RAW 264.7 macrophages to investigate its anti-inflammatory activity. FTIR and DSC studies suggest a predominant presence of α-helix structure for ZN when formulated and also, a strong interaction between components. The stabilization of α-helix by PVMMA or CRM would take place by hydrogen bonds. Although the encapsulation efficiency was high (89%) for ZN/PVMMA Ms, the coating process with Eudragit led to an EE decrease of 62%. Coating of Ms was found to retain a 20% of drug within 6h of release, although a strong initial burst release was observed. Cells viability and apoptosis were not affected when cells were co-incubated with coated Ms with CRM. The exposure of unstimulated cells to Ms did not show any effect on NO and PGE production. However, a reduction in NO and PGE production was obtained when CRM-loaded Ms were co-incubated with stimulated macrophages. Further, this inhibition was significantly higher compared to the decrease obtained when Ms with pure CRM were used in culture, which suggested a synergistic effect of CRM and Ms. Finally, CRM-loaded Ms caused a significant inhibition of analysed pro-inflammatory cytokines (TNFα, IL-1β, NOS2, COX-2) in macrophages stimulated with LPS. All these results confirm the advantageous features of ZN/PVMMA microspheres as a serious alternative for delivering CRM to reduce the inflammatory activity at intestinal regions affected by inflammatory bowel diseases.
这项研究旨在开发一种微粒系统，用于姜黄素（CRM）的肠道靶向递药，CRM 是一种具有抗炎特性的天然多酚。基于玉米醇溶蛋白（ZN）和 Gantrez AN119（PVMMA）的微球（Ms）通过喷雾干燥制备，并涂覆有 pH 敏感聚合物（Eudragit FS30D）。进行了实验设计以优化微粒制剂。通过 SEM、DSC、FTIR、粒径、ζ电位测量和体外 CRM 释放对系统进行了详细的表征。在 LPS 刺激的 RAW 264.7 巨噬细胞中评估了优化的配方，以研究其抗炎活性。FTIR 和 DSC 研究表明，当配方化时，ZN 主要存在α-螺旋结构，并且各成分之间存在强烈的相互作用。PVMMA 或 CRM 通过氢键稳定α-螺旋。尽管 ZN/PVMMA Ms 的包封效率很高（89%），但用 Eudragit 进行包衣过程导致 EE 降低了 62%。发现 Ms 的包衣在释放 6 小时内保留了 20%的药物，但观察到强烈的初始突释。当细胞与载有 CRM 的涂层 Ms 共孵育时，细胞活力和细胞凋亡不受影响。未刺激的细胞暴露于 Ms 不会对 NO 和 PGE 的产生产生任何影响。然而，当用刺激的巨噬细胞共孵育载有 CRM 的 Ms 时，NO 和 PGE 的产生减少。此外，与单独使用载有纯 CRM 的 Ms 相比，这种抑制作用显著更高，这表明 CRM 和 Ms 具有协同作用。最后，载有 CRM 的 Ms 导致 LPS 刺激的巨噬细胞中分析的促炎细胞因子（TNFα、IL-1β、NOS2、COX-2）的显著抑制。所有这些结果证实了 ZN/PVMMA 微球作为将 CRM 递送到减轻受炎症性肠病影响的肠道区域的炎症活性的有效替代物的有利特征。
