Intestinal accumulation of silica particles in a rat model of dextran sulfate sodium-induced colitis

Abstract

Background Ulcerative colitis (UC) is a lifelong inflammatory bowel disease characterized by periods of intense colonic inflammation leading to debilitating symptoms. Delivery methods of current UC treatments are suboptimal and associated with side effects. Silica particles are a potential alternative delivery method for UC therapeutics, given their promising drug-loading and safety profiles. However, it is unknown whether silica particles preferably accumulate at sites of colonic inflammation. This study aimed to correlate silica particle accumulation with colonic inflammation in a rat UC model.

Methods Albino Wistar rats received 4.5% dextran sulfate sodium (DSS) in drinking water (n=6) for 7 days to induce UC. Control rats (n=6) received drinking water only. UC activity was assessed daily using disease activity index. All rats were orally gavaged with silica particles labeled with Alexa-633 tags on day 9, followed by imaging at 3, 6, and 24 h. Silica particle distribution and accumulation were examined using biophotonic imaging, confocal microscopy and fluorescent spectrophotometry. Rats were killed on day 10, with jejunum, ileum and colon collected for histopathological scoring and quantification of fluorescence.

Results Rats treated with DSS had significantly higher UC disease activity (P=0.033) and colonic histopathological scores (P=0.0087) compared to controls. No statistically significant betweengroup differences in silica particle accumulation were seen on live imaging or tissue analysis.

Conclusions No correlation was seen between silica particle accumulation and colonic inflammation. However to draw clear conclusions, further research is required to establish the potential of silica particles as a UC-targeted delivery method.

Keywords Ulcerative colitis, silica particles, dextran sulfate sodium, imaging

Ann Gastroenterol 2019; 32 (6): 584-592