■用于炎症性肠病(IBD)治疗的常规口服制剂不能令人满意,由于药物释放的可控性差以及对胃肠道(GI)炎症部位缺乏特异性。为了克服这些限制,我们开发了一种基于多碳水化合物的纳米系统,具有pH/ROS双重责任和电荷介导的靶向能力,用于IBD特异性药物递送。
■鉴于炎性结肠中ROS的过度产生和阳离子蛋白的过度表达,设计的纳米系统由氧化敏感型环糊精(OX-CD)组成,壳聚糖(CS)和果胶(AHP)。利用OX-CD通过溶剂蒸发法加载地塞米松(DM)。将具有相反电荷的CS和AHP依次涂覆到OX-CD上以通过静电自组装方法产生纳米系统。物理化学性质,稳定性,双重敏感的药物释放行为,细胞毒性,体外研究了细胞摄取和抗炎活性。在溃疡性结肠炎(UC)小鼠中进一步评估纳米系统的体内生物分布和治疗功效。
■获得的AHP/CS/OX-CD-DM纳米系统(ACOC-DM)可以在GIpH环境下保持稳定,并在具有pH/ROS敏感性的炎性结肠中释放药物。与单多糖包被的CS/OX-CD-DM纳米系统(COC-DM)相比,双多糖包被的ACOC-DM在巨噬细胞中表现出更高的细胞摄取和抗炎功效。口服ACOC-DM可以增强UC小鼠的炎症靶向能力和治疗效果。
■这种基于碳水化合物的纳米系统具有pH/ROS双重敏感性和炎症靶向能力,可作为IBD治疗的安全且通用的纳米平台。
UNASSIGNED: Conventional oral formulations for inflammatory bowel disease (IBD) treatment are less than satisfactory, due to the poor controllability of drug release and lack of specificity to the inflammation sites in the gastrointestinal (GI) tract. To overcome these limitations, we developed a multiple carbohydrate-based nanosystem with pH/ROS dual responsibility and charge-mediated targeting ability for IBD-specific drug delivery.
UNASSIGNED: In view of the overproduction of ROS and overexpression of cationic proteins in the inflammatory colon, the designed nanosystem was composed of oxidation-sensitive cyclodextrin (OX-CD), chitosan (CS) and pectin (AHP). OX-CD was utilized to load dexamethasone (DM) by the solvent evaporation method. CS and AHP with opposite charges were sequentially coated onto OX-CD to generate the nanosystems by the electrostatic self-assembly method. The physicochemical properties, stability, dual-sensitive drug release behavior, cytotoxicity, cellular uptake and anti-inflammatory activity were investigated in vitro. In vivo bio-distribution and therapeutic efficacy of the nanosystem were further evaluated in the ulcerative colitis (UC) mice.
UNASSIGNED: The obtained AHP/CS/OX-CD-DM nanosystem (ACOC-DM) could maintain stability under the GI pH environments, and release drug in the inflammatory colon with pH/ROS sensitivity. Dual polysaccharide-coated ACOC-DM exhibited higher cellular uptake and anti-inflammatory efficacy in macrophages than single polysaccharide-coated CS/OX-CD-DM nanosystem (COC-DM). Orally administrated ACOC-DM could enhance inflammation targeting ability and therapeutic efficacy of DM in the UC mice.
UNASSIGNED: This carbohydrate-based nanosystem with pH/ROS dual sensitivity and inflammation targeting capacity may serve as a safe and versatile nanoplatform for IBD therapy.