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Modeling a pH-sensitive Zein-co-acrylic acid hybrid hydrogels loaded 5-fluorouracil and rutin for enhanced anticancer efficacy by oral delivery

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Abstract

The combination of natural and synthetic polymeric materials grafted hydrogels offer great potential as oral therapeutic systems because of its intrinsic biocompatibility, biodegradability, protect labile drugs from metabolism and controlled release properties. Hence, in the present study, we aimed to prepare and optimize oral delivered pH-responsive Zein-co-acrylic acid hydrogels incorporated with 5-fluorouracil (5-Fu) and rutin (Ru) for effective anticancer activity with less toxicity. In this study, graft polymerization technique is adopted to formulate hydrogels with various ratios of Zein, acrylic acid, N, N-methylene bisacrylamide, and ammonium persulphate as an initiator. The optimized formulation was identified based on the cross-linking, chemical interactions, intrinsic viscosity (η), dynamic swelling (Q) at pH 1.2, diffusion coefficient (D), sol–gel fraction (%), and porosity (%). The selected optimized formulation has shown significant improvement in drugs loading and encapsulation efficiency, releasing at pH 1.2 and pH 7.4. Drug release kinetics studies confirmed the controlled release properties of hydrogels. Hydrogels were porous and the drug loading of 5-Fu and Ru was found to be 12.13% and 10.86%, respectively, whereas encapsulation efficiency of 5-Fu and Ru was 89.35% and 81.47%, respectively. Furthermore, form the in vitro cytotoxic screening, it was found that 52.5 µg mL−1 5-Fu and Ru-loaded hydrogel impacted 50% of cell death at 24 h, there by significantly arresting the proliferation of MDA-MB-231 and MCF-7 breast cancer cell lines. Altogether, the optimized pH-responsive hydrogels make them favorable carrier for anticancer drugs for oral delivery.

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Acknowledgements

The authors are grateful to Chancellor, Vice-President, and Vice-chancellor of Kalasalingam Academy of Research and Education (Deemed to be University), Krishnankoil, India, for research fellowships and utilizing research facilities. We thank Mr. P. Kathirvel, Mr. V. Krishnaprabhu Technicians for FTIR, SEM, XRD analysis, Sir CV Raman-KS Krishnan International Research Center, Kalasalingam Academy of Research and Education (Deemed to be University), Krishnankoil, India. We also thank Prof. Z. Maciej Gliwicz, Ms. Ewa Babkiwicz, and Dr. Piotr Maszczyk, Department of Hydrobiology, Faculty of Biology, University of Warsaw, Warszawa, Poland, for timely help and support.

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Authors and Affiliations

  1. Sir CV Raman-KS Krishnan International Research Center, Kalasalingam Academy of Research and Education, Krishnankoil, 626126, India

    Selvaraj Kunjiappan, Suraj Baskararaj, Sankarganesh Arunachalam & Balasubramanian Somasundaram

  2. Department of Research and Development, Saraswathi Institute of Medical Sciences, NH-24, Anwarpur, Pilkhuwa, Hapur, Uttar Pradesh, 245304, India

    Panneerselvam Theivendran

  3. School of Automotive and Mechanical Engineering, Kalasalingam Academy of Research and Education, Krishnankoil, 626126, India

    Bathrinath Sankaranarayanan

  4. School of Mechanical Engineering, Vellore Institute of Technology, Vellore, 632014, India

    Ponnusamy Palanisamy

  5. Department of Pharmaceutical Chemistry, MNR College of Pharmacy, Fasalwadi, Sangareddy, Telangana, 502294, India

    Govindaraj Saravanan

  6. Department of Pharmacy, Birla Institute of Technology and Science, Pilani, 333031, India

    Murugesan Sankaranarayanan

  7. Department of Pharmaceutics, JSS College of Pharmacy, Rockland’s, Ooty, 643001, India

    Jawahar Natarajan

  8. Department of Pharmaceutical Biotechnology, JSS College of Pharmacy, Rockland’s, Ooty, 643001, India

    Ashish Wadhwani

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  1. Selvaraj Kunjiappan
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Contributions

SK, PT, SB, and BS designed research; SK, SB, PP, GS, JN, and AW performed research; SM, SA, and BS contributed new reagents or analytical tools. All authors read and approved the final manuscript.

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Correspondence to Selvaraj Kunjiappan.

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Kunjiappan, S., Theivendran, P., Baskararaj, S. et al. Modeling a pH-sensitive Zein-co-acrylic acid hybrid hydrogels loaded 5-fluorouracil and rutin for enhanced anticancer efficacy by oral delivery. 3 Biotech 9, 185 (2019). https://doi.org/10.1007/s13205-019-1720-x

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