5-ASA-loaded SiO2 nanoparticles-a novel drug delivery system targeting therapy on ulcerative colitis in mice.

The targeting of 5-aminosalicylic acid (5-ASA), a first-line therapeutic agent for mild to moderate active ulcerative colitis (UC), to the site of inflammation has remained a challenge and an unmet requirement in the treatment of UC. However, nanoscale carriers for targeted drug delivery are promising for pharmacotherapy, and nanoparticles improve the pharmacokinetics of the loaded therapeutics based on their physical properties. To design and prepare 5‑ASA‑loaded silicon dioxide nanoparticles (5‑ASA‑SiO2 NPs), a micro‑emulsion method was conducted, and their respective therapeutic effects were validated in a mouse model of UC. Cytotoxicity of 5‑ASA‑SiO2 NPs was detected in vitro using the Cell Counting Kit‑8 method. The therapeutic effect of 5‑ASA‑SiO2 NPs was assessed based on their disease activity index (DAI), colon histopathology, myeloperoxidase (MPO) and levels of tumor necrosis factor‑α (TNF‑α) and interleukin‑6 (IL‑6). SiO2 NPs were successfully prepared, and cytotoxicity of 5‑ASA‑SiO2 NPs was identified as being similar to 5‑ASA and SiO2 NPs. DAI and colonic histopathology scores in the normal dosage, high dosage and the 5‑ASA‑SiO2 NP groups demonstrated a significant improvement when compared with the model group. DAI in the high dosage and 5‑ASA‑SiO2 NP groups also demonstrated a significant improvement when compared with the normal dosage group. However, MPO, serum IL‑6 and TNF‑α levels in normal dosage, high dosage and 5‑ASA‑SiO2 NPs groups were significantly lower than in the model group, and these indexes in the high dosage group and 5‑ASA‑SiO2 NP group were significantly lower than that in the normal dosage group. Expression of IL‑6 and TNF‑α mRNA in colonic mucosa in the normal dosage, high dosage and 5‑ASA‑SiO2 NP group was significantly lower than that in the model group. Colonic mucosal IL‑6 and TNF‑α mRNA expression in the high dosage and 5‑ASA‑SiO2 NP groups was significantly lower than that in the normal dosage group (P<0.05). In conclusion, 5‑ASA‑SiO2 NPs are a selective drug release system that target the inflamed colon, characteristics of UC, and can greatly increase therapeutic efficacy in UC.