Fabrication of pH-dependent solid dispersion for oral colon-targeted delivery of notoginsenoside R1 and its protective effects on ulcerative colitis mice

作者：Hongyun Tie, Yaru Wang, Yunxia Shang, Manlin Li, Xiaohui Wei, Zhengtao Wang · 发表于：Heliyon · 年份：2023 · DOI：10.1016/j.heliyon.2023.e20280 · 被引用次数：8 · 研究领域：Pharmacological Effects of Natural Compounds、Drug Transport and Resistance Mechanisms、Ginseng Biological Effects and Applications

Notoginsenoside R1 (R1), which originated from the rhizomes and roots of Panax notoginseng, is classified as a Biopharmaceutical Classification System class III drug with good solubility but poor oral absorption. Although R1 can alleviate the inflammation of dextran sulfate sodium (DSS)-induced colitis in mice, the problem of acid degradation and low bioavailability limit its application. The purpose of this study was aimed to design one kind of pH-dependent solid dispersion for oral colon-targeted delivery of R1. Using Eudragit S100 (ES 100) and PEG 4000 as the pH-dependent carriers, R1 solid dispersion (R1-SD) was fabricated by solvent evaporation method. Scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction analysis indicated that R1-SD was completely formed, the surface was smooth surface and the strip crystal structure of R1 disappeared. The in vitro release profile of R1-SD (R1-ES100-PEG4000, 1:7:1, weight ratio) exhibited that R1-SD was not released in media simulating the gastric condition (pH 1.2), but better release characteristics of the drug could be obtained in media simulating the intestinal condition (less than 30% in pH 6.8 buffer and more than 90% in pH 7.6 condition). The in vitro colon absorption test showed that the absorption rate and cumulative release of R1-SD were higher than those of R1. R1-SD and R1 had apparent protective effect on colon shortening, inflammatory infiltrating tissue injury, weight loss, diarrhe...