title: 5-ASA-loaded SiO2 nanoparticles-a novel drug delivery system targeting therapy on ulcerative colitis in mice.
abstract: 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.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Liver Disease, The Sixth People's Hospital of Shenyang, Shenyang, Liaoning 110000, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Yingde
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019804:Mesalamine / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009195:Peroxidase / Q000378:metabolism; D012720:Severity of Illness Index; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D019804:Mesalamine; D012822:Silicon Dioxide; D009195:Peroxidase