Effects of Silibin Nanocapsules on Acetic Acid Induced Ulcerative Colitis in Rats

Silibin is the major (70–80%) and the most active biological flavonolignan of silymarin with antioxidant and anti-inflammatory effects. Studies have shown that nanoparticles can effectively be swallowed by macrophages which are associated with inflammation procedure of ulcerative colitis. In addition, further reducing the particle size increases particle uptake into the intestinal cells and the particles could be deposited more effectively on affected areas. In the present study, nanoparticles of silibin were designed to evaluate their effectiveness on ulcerative colitis in rats. Test nanoparticles consisted of 15 mg of silibin loaded in 15 mg of poly(ethyl acrylate-co-methyl methacrylate-co-trimethyl ammonium ethyl methacrylate) polymer with average particle size of 109 nm which had been coated by 20% w/w of poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid) polymer in order to deliver nanoparticles to colon specifically. Five separate groups of rats were fasted for 36 hours and then, colitis was induced with 2 ml of acetic acid 4%. Treatments were made for 5 days, once a day, started 2 hours before colitis induction. The designed groups were: nanocapsules containing 75 mg/kg silibin, nanocapsules without silibin, dexamethasone (1 mg/kg), normal saline (2 ml/kg) and normal group. 24 hours after the last administration, colon tissue was removed; macroscopic and histopathologic assessment, also determination of myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) levels were conducted. Silibin nanocapsules were effective to diminish inflammation and ulcer severity while it was not able to reduce ulcer area statistically. Weight/length ratio in dexamethason and silibin nanocapsule group was close to that in normal group. Microscopic assessment of silibin nanocapsule group showed a mild to moderate inflammation of mucosa and minimal crypt damage as the values were significantly different from those of control group. Treatment with silibin nanocapsules resulted in decreasing of myeloperoxidase activity and also both levels of IL-6 and TNF-α compared to control group. Poly (ethyl acrylate-co-methyl methacrylate-co-trimethyl ammonium ethyl methacrylate) nanocapsules of silibin could be considered as a suitable alternative for present drugs with anti-colitis property. However, more studies are needed to support this hypothesis for clinical use.