Improving silymarin oral bioavailability using silica-installed redox nanoparticle to suppress inflammatory bowel disease

• Published in: Journal of controlled release 2021-03, Vol.331, p.515-524
• Main Authors: Nguyen, Thu-Ha Thi, Trinh, Nhu-Thuy, Tran, Han Ngoc, Tran, Hao Thi, Le, Phong Quoc, Ngo, Dai-Nghiep, Tran-Van, Hieu, Van Vo, Toi, Vong, Long Binh, Nagasaki, Yukio
• Format: Article
• Language: English
• Subjects: Inflammatory bowel disease; Pharmacokinetics; Poor-water soluble drug; Redox nanoparticles; ROS; Silymarin
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2020.10.042

Chronic inflammatory diseases such as inflammatory bowel diseases (IBD), which are strongly related to the overproduction of reactive oxygen species (ROS), have become more threatening to health. Silymarin is an active compound with the effect of expressing anti-inflammatory activity; however, it exhibits poor bioavailability due to the rapid metabolism and secretion, low permeability across the intestinal epithelial cells, and poor water solubility. In this study, we developed silica-containing redox nanoparticles (siRNP) with 50–60 nm in diameter to improve the bioavailability of silymarin by improving its uptake into the bloodstream and delivery to the targeted tissues of the colon. Silymarin-loaded siRNP (SM@siRNP) significantly increased the antioxidant capacity and anti-inflammatory efficacy in vitro by scavenging 2,2-diphenyl-1-picrylhydrazyl free radical and suppressing nitric oxide and pro-inflammatory cytokines as compared to the other treatments such as free silymarin, siRNP, and silymarin-loaded si-nRNP (the control nanoparticle without ROS scavenging property). Orally administered SM@siRNP significantly improved the bioavailability of silymarin and its retention in the colonic mucosa. The anti-inflammatory effects of SM@siRNP were also investigated in dextran sodium sulfate (DSS)-induced colitis in mice and it was observed that SM@siRNP treatment significantly improved the damage in the colonic mucosa of DSS colitis mice as compared to the other treatments. The results in this study indicate that SM@siRNP is a promising nanomedicine for enhancing the anti-inflammatory activity of silymarin and has a high potential for the treatment of IBD. [Display omitted] •Silica-containing redox nanoparticle (siRNP) was designed for deliver hydrophobic drug (silymarin) in treating colitis.•siRNP significantly improved the antioxidant and anti-inflammatory activities of free drug in vitro.•siRNP inhibited the degradation of silymarin induced by reactive oxygen species.•siRNP enhanced the bioavailability of silymarin and it retention in colonic mucosa after oral administration.•Oral administration of silymarin-loaded siRNP effectively suppressed the inflammation in the colitis mice