1. A nitrophenyl-based prodrug type for colorectal targeting of prednisolone, budesonide and celecoxib.
- Author
-
Marquez Ruiz JF, Kedziora K, Pigott M, Keogh B, Windle H, Gavin J, Kelleher DP, and Gilmer JF
- Subjects
- Antineoplastic Agents therapeutic use, Antineoplastic Agents toxicity, Budesonide therapeutic use, Budesonide toxicity, Caco-2 Cells, Celecoxib, Cell Membrane Permeability drug effects, Clostridium perfringens drug effects, Colorectal Neoplasms drug therapy, Cyclooxygenase 2 Inhibitors chemistry, Cyclooxygenase 2 Inhibitors therapeutic use, Cyclooxygenase 2 Inhibitors toxicity, Humans, Lactones chemistry, Nitroreductases metabolism, Prednisolone therapeutic use, Prednisolone toxicity, Prodrugs therapeutic use, Prodrugs toxicity, Pyrazoles therapeutic use, Pyrazoles toxicity, Sulfonamides therapeutic use, Sulfonamides toxicity, Antineoplastic Agents chemistry, Budesonide chemistry, Nitrobenzenes chemistry, Prednisolone chemistry, Prodrugs chemistry, Pyrazoles chemistry, Sulfonamides chemistry
- 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., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF