Synthesis and bio-evaluation of xylan-5-fluorouracil-1-acetic acid conjugates as prodrugs for colon cancer treatment

Article abstract of DOI:10.1016/j.carbpol.2016.09.096

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.

Full text of DOI:10.1016/j.carbpol.2016.09.096

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Accepted Manuscript
Title: Synthesis and bio-evaluation of
xylan-5-fluorouracil-1-acetic acid conjugates as prodrugs for
colon cancer treatment
Author: Sauraj S. Uday Kumar P. Gopinath Yuvraj Singh Negi
PII:
S0144-8617(16)31157-2
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.carbpol.2016.09.096
CARP 11734
To appear in:
Received date:
Revised date:
Accepted date:
4-6-2016
25-9-2016
29-9-2016
Please cite this article as: Sauraj, ., Kumar, S Uday., Gopinath, P., &
Negi, Yuvraj Singh., Synthesis and bio-evaluation of xylan-5-fluorouracil-1-acetic
acid conjugates as prodrugs for colon cancer treatment.Carbohydrate Polymers
http://dx.doi.org/10.1016/j.carbpol.2016.09.096
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Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Manuscript
Synthesis and bio-evaluation of xylan-5-fluorouracil-1-acetic acid conjugates
as prodrugs for colon cancer treatment
Sauraja, S Uday Kumarb, P.Gopinathb,c Yuvraj Singh Negi*a
aDepartment of Polymer and Process Engineering
bNanobiotechnology Laboratory, Centre for Nanotechnology,
c Department of Biotechnology,
Indian Institute of Technology Roorkee, Roorkee, Uttarakhand-247667, India.
*Corresponding author: Tel. +91-0132-2714303; Fax. +91-0132-2714311
E.mail: yuvrajnegi@gmail.com

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Revised Highlights:
 Xyl-5-FUAC conjugates were synthesized as prodrugs for colon specific drug
delivery
 Higher amount of drug was released from the conjugates in presence of colonic
contents
 Xyl-5-FUAC conjugates shows better cytotoxicity than free drug

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
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% was 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.
Keywords: Xylan, 5-fluorouracil-1-acetic acid (5-FUAC), drug release, gastrointestinal contents,
cell cytotoxicity