Investigation of interaction of polyphenols with biomacromolecule and their anti cancer antimicrobial liposomal formulation

Abstract

This study primarily aims in optimizing use of flavonoids in the cancer therapy. The anticancer efficacy of our three chosen flavonoids, namely quercetin, luteolin and apigenin were determined upon their interactions with biomacromolecules. Quercetin has shown highest binding efficiency with ct DNA and binds well at pH 5. Apigenin proved to be a better intercalator. Cytotoxicity of flavonoids by inducing DNA damage increased in the presence of copper. Quercetin has the maximum inhibitory effect on the antioxidant enzyme catalase, but the effect was reversed by the presence of copper. Inhibition of catalase will result in the generation of ROS that can induce apoptosis in cancer cells establishing a mechanism of the pro-oxidant effect of these polyphenols. Since copper modulates the interaction of ct DNA and catalase with quercetin, influence of metal ion upon interaction of quercetin with HSA was studied by coating quercetin over silver nano particles (AgNPs). It is observed that quercetin coated on AgNP have a better binding efficiency than free quercetin which was due to small size (66 nm), uniform coating of flavonoid on the nano particle and changes in properties that favours deep penetration of quercetin in the protein. The use of quercetin as a chemotherapeutic drug is limited by its poor bioavailability. Quercetin along with doxorubicin and EGCG is encapsulated in the liposome exploiting the ampiphilic property of liposome. The liposome is PEGylated to improve the stability of the formulation. The liposome is made positively charged by coating the formulated nano particle with histone. Size of the formulation obtained is about 342 nm. The formulation demonstrated anticancer activity on K562 cells with reduced effect on normal lymphocytes. Along with it the formulation is useful in eradicating secondary infections in cancer patients as it displays an antibiotic action by inhibiting the growth of E. coli and Staphylococcus aureus. newline