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  • br P Agostinis K Berg K Cengel

    2019-10-24


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    Contents lists available at ScienceDirect
    Biomedicine & Pharmacotherapy
    journal homepage: www.elsevier.com/locate/biopha
    Original article
    A novel rutin-fucoidan complex based phytotherapy for cervical cancer T
    through achieving enhanced bioavailability and cancer cell apoptosis
    Murugesan Sathiya Deepikaa, Ramar Thangamb, Thankaraj Salammal Sheenad, Rajendran Sasirekhae, Srinivasan Sivasubramanianc, Manikandan Dinesh Babua, Kulandaivel Jeganathand, Ramasamy Thirumurugana,
    a Laboratory of Aquabiotics/Nanoscience, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India
    b CSIR-Central Leather Research Institute, Chennai 600 020, Tamil Nadu, India
    c King Institute of Preventive Relebactam Medicine & Research, Chennai 600 032, Tamil Nadu, India
    d Centre for Nanoscience and Nanotechnology, Department of Physics, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India
    e Department of Marine Science, School of Marine Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India
    Keywords:
    Rutin-Fucoidan (Ru-Fu)
    HeLa cells
    Cytotoxicity
    Apoptosis
    Cell cycle arrest
    Hemolysis 
    Recent studies on flavonoids forming complexes with macromolecules attract researchers due to their enhanced bioavailability as well as chemo-preventive efficacy. In this study, a flavonoid rutin (Ru) is non-covalently complexed with fucoidan (Fu) using the functional groups to obtain a therapeutic polymeric complex over-coming the limitations of bioavailability of rutin. The prepared novel rutin-fucoidan (Ru-Fu) complex is char-acterized for spectroscopic features, particle size and distribution analysis by DLS. It is shown that the complex displayed the nanostructural features that are different from that of the usual rutin-fucoidan mixture. The studies on drug release profiles at different pH (5.5, 6.8 and 7.4) show that the sustained release of compounds from complex occurs preferentially at the desired endosomal pH (5.5). Further, the chemopreventive potential of Ru-Fu complex is investigated against HeLa cells by cellular apoptotic assays and flow cytometric analysis. It showed that the complex is able to disrupt cell cycle regulation and has the ability to induce cellular apoptosis via nuclear fragmentation, ROS generation and mitochondrial potential loss. In vitro cell viability assay with Ru-Fu complex shows that the complex is biocompatible on normal cells. The hemolysis assay also reveals that the complex does not release hemoglobin from human red blood cells (RBCs). Thus, the study is envisaged to open up interests for developing such formulations against cervical cancer and other cancers.