A novel rutin-fucoidan complex based phytotherapy for cervical cancer through achieving enhanced bioavailability and cancer cell apoptosis

Abstract

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 overcoming the limitations of bioavailability of rutin. The prepared novel rutin-fucoidan (Ru-Fu) complex is characterized 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.