Dpto. Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, 41012-Seville, Spain.
PRO2TECS. Departamento de Ingeniería Química, Facultad de Ciencias Experimentales, Campus El Carmen⁻21071-Huelva, Spain.
Int J Mol Sci. 2019 Jan 18;20(2):398. doi: 10.3390/ijms20020398.
In the present work, we demonstrate the preparation of chitosan-based composites as vehicles of the natural occurring multi-drug resveratrol (RES). Such systems are endowed with potential therapeutic effects on inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis, through the sustained colonic release of RES from long-lasting mucoadhesive drug depots. The loading of RES into nanoparticles (NPs) was optimized regarding two independent variables: RES/polymer ratio, and temperature. Twenty experiments were carried out and a Box⁻Behnken experimental design was used to evaluate the significance of these independent variables related to encapsulation efficiency (EE). The enhanced RES EE values were achieved in 24 h at 39 °C and at RES/polymer ratio of 0.75:1 /. Sizes and polydispersities of the optimized NPs were studied by dynamic light scattering (DLS). Chitosan (CTS) dispersions containing the RES-loaded NPs were ionically gelled with tricarballylic acid to yield CTS-NPs composites. Macro- and microscopic features (morphology and porosity studied by SEM and spreadability), thermal stability (studied by TGA), and release kinetics of the RES-loaded CTS-NPs were investigated. Release patterns in simulated colon conditions for 48 h displayed significant differences between the NPs (final cumulative drug release: 79⁻81%), and the CTS-NPs composites (29⁻34%).
在本工作中，我们展示了壳聚糖基复合材料的制备，作为天然存在的多药物白藜芦醇（RES）的载体。通过从长效粘膜粘附药物库中持续释放 RES，这些系统具有治疗炎症性肠病（IBD）的潜力，如克罗恩病（CD）和溃疡性结肠炎。关于两个独立变量（RES/聚合物的比例和温度）对 RES 进行了优化负载到纳米颗粒（NPs）中。进行了 20 项实验，并使用 Box⁻Behnken 实验设计来评估这些与包封效率（EE）相关的独立变量的重要性。在 39°C 和 RES/聚合物比例为 0.75:1 的条件下，在 24 小时内实现了增强的 RES EE 值。优化的 NPs 的大小和多分散性通过动态光散射（DLS）进行了研究。用三羟甲基丁酸将含有负载 RES 的 NPs 的壳聚糖（CTS）分散体离子交联，以得到 CTS-NPs 复合材料。对负载 RES 的 CTS-NPs 的宏观和微观特征（通过 SEM 研究的形态和孔隙率以及可扩展性）、热稳定性（通过 TGA 研究）和释放动力学进行了研究。在模拟结肠条件下释放 48 小时后， NPs（最终累积药物释放：79⁻81%）和 CTS-NPs 复合材料（29⁻34%）之间显示出显著差异。
