DEVELOPMENT OF A TARGETED NANOGEL SYSTEM BASED ON FUCOIDAN-POLOXAMER CONJUGATED FOLIC ACID FOR CO-DELIVERY OF CISPLATIN AND CURCUMIN FOR BREAST CANCER TREATMENT

Abstract

The self-assemble micelle for co-delivery of Curcumin (Cur) and Cisplatin (Cis) has been developed to enhance anticancer efficacy by the improved drug solubility to cell membrane absorption, thereby increase their bioavailability leading to reduced side effects. Meanwhile, folic acid has gained popularity as an active ligand targeted-tumor tissue via the specific interaction with folate receptors overexpressed on tumor cells. Therefore, in this work, the provision of folic acid-functionalized fucoidan-poloxamer (P403 and P407) were co-loaded with Cis and Cur, with the purpose of improved synergism effect their therapeutic efficacy. The characterization nanogels were evaluated through proton nuclear technique (1H-NMR), Fourier-transform infrared spectroscopy (FT-IR) exhibiting the similarity in the structure between FA-Fud-P403 and FA-Fud P407. However, the FA-Fud-P403 showed a lower CMC, with smaller particle size compared to FA-Fud-P407. Thus, the co-encapsulation of drugs into FA-Fud-P403 was more efficient than FA-Fud-P407, with 47.146% for Cis and 95.723% for Cur of the drug loading capacity of FA-Fud-P403, followed by 41.201% for Cis and 74.831% for Cur loaded into FA-Fud-P407. Notably, the investigation of controlled sustain Cur/Cis released from the nanogels indicated for the burst release at acidic pH 5.5 micking to the tumor areas. In in vitro cell uptake, the dual-drug nanogels exhibited the lower cytotoxicity toward breast cancer cell line (MCF-7) compared to free Cis treatment at the same concentration. In addition, the two-combinational drugs loaded into nanogel showed the greater cell cytotoxicity than single-drug, where the anticancer efficiency of FA-Fud P403 was determined greater than that of FA-Fud-P407, highlighting the potential synergism effect of Cur to optimize the single-dose treatment and minimize the adverse effects of conventional methods.