Department of Chemical Engineering and Institute of Biomedical Engineering, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu, Taiwan ROC.
Department of Pathology, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan ROC.
Biomaterials. 2018 Nov;182:289-298. doi: 10.1016/j.biomaterials.2018.07.044. Epub 2018 Aug 16.
Inflammatory bowel disease (IBD) is an intestinal inflammatory disorder. Exogenous hydrogen sulfide (HS) donors such as diallyl trisulfide (DATS) have been used as anti-inflammatory mediators. However, an ideal method of administering DATS has yet to be established owing to its poor water solubility. Herein, a self-spray coating system that is derived from a DATS-loaded capsule with foaming capability (CAP-w-FC) is proposed for treating colitis. Following the rectal administration of CAP-w-FC into rats bearing colitis and its subsequent dissolution in the intestinal fluid, a spray coating system is self-assembled in situ. This system greatly promotes the dissolution of the poorly water-soluble DATS by producing nano-scaled micellar particles that are sprayed onto the large luminal surface of the colorectal tract. Following the internalization of the micellar particles by colon epithelial cells, their loaded DATS reacts with intracellular glutathione to yield HS. This exogenous HS then diffuses through plasma membranes to carry out its biological functions, including suppressing the overproduction of pro-inflammatory cytokines, inhibiting the adhesion of macrophages on the vascular endothelium, and repairing colonic inflamed tissues. Analytical results demonstrate that this self-spray coating system may be used as a unique drug delivery technique for covering the large colorectal surface to treat IBD.
炎症性肠病(IBD)是一种肠道炎症性疾病。外源性硫化氢(HS)供体,如二烯丙基三硫化物(DATS),已被用作抗炎介质。然而,由于其水溶性差,尚未建立理想的 DATS 给药方法。本文提出了一种源自具有发泡能力的载 DATS 胶囊的自喷涂涂层系统(CAP-w-FC),用于治疗结肠炎。在将 CAP-w-FC 直肠给药到患有结肠炎的大鼠体内并使其随后在肠液中溶解后,喷涂系统在原位自组装。该系统通过产生纳米级胶束颗粒来极大地促进了难溶于水的 DATS 的溶解,这些胶束颗粒被喷涂到大肠腔的大腔表面上。胶束颗粒被结肠上皮细胞内化后,其负载的 DATS 与细胞内谷胱甘肽反应生成 HS。这种外源性 HS 然后通过质膜扩散以发挥其生物学功能,包括抑制促炎细胞因子的过度产生、抑制巨噬细胞在血管内皮上的黏附以及修复结肠炎症组织。分析结果表明,这种自喷涂涂层系统可用作覆盖大肠腔表面的独特药物递送技术,用于治疗 IBD。