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

Abstract

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-ES 100-PEG 4000, 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 phosphate-buffered saline 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, diarrhea, blood stool in mice with ulcerative colitis induced by DSS, and the protective effect of R1-SD was better than that of R1, which indicated R1-SD has good practical application prospects.

Keywords

• Notoginsenoside R1
• Solid dispersion
• Colon-targeted drug delivery system
• Ulcerative colitis