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Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Authors Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

Received 25 February 2012

Accepted for publication 24 May 2012

Published 15 November 2012 Volume 2012:7 Pages 5769—5779

DOI https://doi.org/10.2147/IJN.S31201

Review by Single-blind

Peer reviewer comments 4

N Ashwanikumar,1,* Nisha Asok Kumar,2,* S Asha Nair,2 GS Vinod Kumar1

1Chemical Biology, 2Cancer Research Programme, Rajiv Gandhi Center for Biotechnology, Poojappura, Thiruvananthapuram, Kerala, India

*These authors contributed equally to this work

Abstract: Methacrylic-based copolymers in drug-delivery systems demonstrate a pH-sensitive drug-releasing behavior in the colon. In this study, copolymers of methacrylic acid and 2-ethyl hexyl acrylate were prepared using a microemulsion polymerization technique. The purified copolymer was characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and differential scanning calorimetry. 5-Fluorouracil (5-FU) was entrapped within methacrylic-based copolymers by a solvent evaporation method. The size of the nanogels formed was characterized by transmission electron microscopy and atomic force microscopy. In vitro drug-release studies using phosphate-buffered saline at different pH levels demonstrated the sustained release of 5-FU and its pH dependence. Cell proliferation assay of a human colon tumor colon cancer cell line (HCT-116) was performed and showed that the nanogels containing 5-FU exhibited considerable cytotoxicity in comparison with free 5-FU. Cell uptake of the nanogels was also monitored using confocal microscopy. Western blot analysis and flow cytometry studies confirmed that the nanogels could be successfully used as an efficient vector for pH-sensitive and controlled delivery of drugs specifically targeted to the colon.

Keywords: 5-FU, methacrylic polymer, colon cancer, nanogel

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