title: Hemocompatible curcumin-dextran micelles as pH sensitive pro-drugs for enhanced therapeutic efficacy in cancer cells.
abstract: Curcumin, a component in spice turmeric, is renowned to possess anti-cancer therapeutic potential. However, low aqueous solubility and instability of curcumin which subsequently affects its bioavailability pose as major impediments in its translation to clinical application. In this regard, we focused on conjugating hydrophobic curcumin to the hydrophilic backbone of dextran via succinic acid spacer to design a pro-drug. The structural confirmation of the conjugates was carried out using FTIR and (1)H NMR spectroscopy. Critical micelle measurement affirmed the micelle formation of the pro-drug in aqueous media. The size distribution and zeta potential of the curcumin-dextran (Cur-Dex) micelles were determined using dynamic light scattering technique. The micellar architecture bestowed curcumin negligible susceptibility to degradation under physiological conditions along with enhanced aqueous solubility. Biocompatibility of the micelles was proved by the blood component aggregation and plasma protein interaction studies. In vitro release studies demonstrated the pH sensitivity release of curcumin which is conducive to the tumour micro environment. Profound cytotoxic effects of Cur-Dex micelles in C6 glioma cells were observed from MTT and Live/Dead assay experiments. Moreover, enhanced cellular internalization of the Cur-Dex micelles compared to free curcumin in the cancer cells was revealed by fluorescence microscopy. Our study focuses on the feasibility of Cur-Dex micelles to be extrapolated as promising candidates for safe and efficient cancer therapy.
authors.affiliation: Division of Biosurface Technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Poojappura, Thiruvananthapuram 695012, Kerala, India.
authors.forename: Radhika
authors.initials: R
authors.lastname: Raveendran
authors.affiliation: Division of Biosurface Technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Poojappura, Thiruvananthapuram 695012, Kerala, India; Innovations and Research, Trivitron Healthcare Pvt. Ltd, IITM Research Park, Chennai, India.
authors.forename: G S
authors.initials: GS
authors.lastname: Bhuvaneshwar
authors.affiliation: Division of Biosurface Technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Poojappura, Thiruvananthapuram 695012, Kerala, India; Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India. Electronic address: drsharmacp@yahoo.com.
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Sharma
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry*; D001773:Blood Cells / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003474:Curcumin / Q000031:analogs & derivatives*; D003911:Dextrans / Q000737:chemistry*; D006461:Hemolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D011355:Prodrugs / Q000009:adverse effects / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D008823:Micelles; D011355:Prodrugs; D003474:Curcumin
keywords: Cellular uptake; Curcumin; Dextran; Micelles; Self-assembly