title: Synthesis and bio-evaluation of xylan-5-fluorouracil-1-acetic acid conjugates as prodrugs for colon cancer treatment.
abstract: In the present study, xylan-5-fluorouracil-1-acetic acid (Xyl-5-FUAC) conjugates as colon specific prodrugs were synthesized and evaluated by in-vitro release study. The chemical stability of the conjugates was performed in acidic (pH 1.2) and basic buffers (pH 7.4), which showed their stability in upper gastrointestinal tract. The in-vitro drug release profiles of the conjugates were studied in the presence of rat's gastrointestinal contents. The results showed that the low amounts of drug 3-4% and 5-7% were released in gastric and small intestine contents respectively, while 53-61% of the drug was released in cecum and colonic contents. The cytotoxicity studies of the conjugates were also evaluated on human colorectal cancer cell line (HTC-15 and HT-29), which showed that the conjugates are more cytotoxic than the free drug. Therefore the results reveal that Xyl-5-FUAC conjugates are potential candidates for colon specific drug delivery in the treatment of colonic cancer with minimal undesirable side effects.
authors.affiliation: Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
authors.lastname: Sauraj
authors.affiliation: Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
authors.forename: S Uday
authors.initials: SU
authors.lastname: Kumar
authors.affiliation: Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India; Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
authors.forename: P
authors.initials: P
authors.lastname: Gopinath
authors.affiliation: Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India. Electronic address: yuvrajnegi@gmail.com.
authors.forename: Yuvraj Singh
authors.initials: YS
authors.lastname: Negi
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy*; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D011355:Prodrugs / Q000494:pharmacology*; D051381:Rats; D014990:Xylans / Q000494:pharmacology*
chemical_list: D011355:Prodrugs; D014990:Xylans; D019342:Acetic Acid; D005472:Fluorouracil
keywords: 5-Fluorouracil-1-acetic acid (5-FUAC); Cell cytotoxicity; Drug release; Gastrointestinal contents; Xylan