title: A nitrophenyl-based prodrug type for colorectal targeting of prednisolone, budesonide and celecoxib.
abstract: Celecoxib is a COX-2 inhibitor drug that can be used to reduce the risk of colorectal adenocarcinoma. Glucocorticoids are used in the treatment of inflammatory bowel disease. A limitation to the use of both drug types is that they undergo absorption from the intestinal tract with serious side effects. The prodrug systems introduced here involve forming a nitro-substituted acylsulfonamide group in the case of celecoxib and a nitro-substituted 21-ester for the glucocorticoids. Drug release is triggered by the nitro reductase action of the colonic microflora, liberating a cyclization competent species. The release of the active parent drugs was evaluated in vitro using Clostridium perfringens and epithelial transport through Caco-2 monolayer evaluation was carried out to estimate the absorption properties of the prodrugs compared to the parental drugs.
authors: School of Pharmacy and Pharmaceutical Sciences, Trinity College, Dublin 2, Ireland.
authors: Juan F
authors: JF
authors: Marquez Ruiz
authors: Kinga
authors: K
authors: Kedziora
authors: Maria
authors: M
authors: Pigott
authors: Brian
authors: B
authors: Keogh
authors: Henry
authors: H
authors: Windle
authors: Jason
authors: J
authors: Gavin
authors: Dermot P
authors: DP
authors: Kelleher
authors: John F
authors: JF
authors: Gilmer
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D019819:Budesonide / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D018938:Caco-2 Cells; D000068579:Celecoxib; D002463:Cell Membrane Permeability / Q000187:drug effects; D003016:Clostridium perfringens / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D007783:Lactones / Q000737:chemistry; D009578:Nitrobenzenes / Q000737:chemistry*; D009601:Nitroreductases / Q000378:metabolism; D011239:Prednisolone / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D011355:Prodrugs / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D011720:Pyrazoles / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D013449:Sulfonamides / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D009578:Nitrobenzenes; D011355:Prodrugs; D011720:Pyrazoles; D013449:Sulfonamides; D019819:Budesonide; D011239:Prednisolone; C036077:nitrobenzene; D009601:Nitroreductases; D000068579:Celecoxib