Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
Division of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
ACS Appl Bio Mater. 2021 Mar 15;4(3):2335-2341. doi: 10.1021/acsabm.0c01105. Epub 2021 Feb 11.
Butyrate has been attracting attention for the suppression of inflammatory bowel disease (IBD). However, clinical trials of butyrate for IBD treatment have resulted in controversial outcomes, likely owing to the adverse effect of butyrate on the intestinal epithelium that was observed at high butyrate concentrations. Herein, we propose polyvinyl butyrate (PVBu) nanoparticles (NPs) as butyrate donors for delivery to the lower part of the intestine for the treatment of colitis. The PVBu NPs suppressed the inflammatory activation of macrophages , although sodium butyrate inversely further activated macrophages. Oral administration of NPs did not change the luminal concentration of free butyrate; however, NPs showed a therapeutic effect on a colitis mouse model. In addition, incorporation of vitamin D into the NPs enhanced the therapeutic effect on colitis. Hence, PVBu NPs are a promising therapeutic for IBD treatment, not only as a butyrate donor but also as a carrier for hydrophobic drugs like vitamin D.
丁酸盐因其抑制炎症性肠病(IBD)的作用而受到关注。然而,丁酸盐治疗 IBD 的临床试验结果却存在争议,这可能是由于在高丁酸盐浓度下观察到丁酸盐对肠上皮的不良影响。在此,我们提出将聚丁烯酸丁酯(PVBu)纳米粒子(NPs)作为丁酸供体,用于递送至肠道下部以治疗结肠炎。PVBu NPs 抑制了巨噬细胞的炎症激活,而丁酸钠则相反地进一步激活了巨噬细胞。NPs 的口服给药并未改变腔内游离丁酸盐的浓度;然而,NPs 对结肠炎小鼠模型显示出治疗效果。此外,将维生素 D 掺入 NPs 中增强了对结肠炎的治疗效果。因此,PVBu NPs 是一种有前途的 IBD 治疗药物,不仅可以作为丁酸供体,还可以作为维生素 D 等疏水性药物的载体。