SUCCINYLATED CURCUMIN LOADED IN MANNOSYLATED CHITOSAN NANOPARTICLES FOR COLON CANCER THERAPY

Abstract

Colon cancer (CRC) is the second leading cause of death and the third most diagnosed type worldwide. Although curcumin (CUR) has potent anticancer activity, it suffers from low solubility, bioavailability, and instability. This study aims to conjugate CUR to succinic anhydride (SA) and then formulate in mannosylated-chitosan nanoparticles (CUR.SA-NPs). The formulation was optimized in comparison to curcumin only in the same delivery system. Dynamic light scattering (DLS) studies disclosed a higher size of CUR-NPs (268 ± 6 nm) and CUR.SA-NPs (342 ± 4.6 nm) compared to empty delivery system, CM-NPs, (101 ± 4.3 nm). Conversely, the zeta-potential was reduced from 41.2 ± 0.15 mV to 11 ± 0.75 mV and 13.6 ± 0.8 mV for CUR-NPs and CUR.SA-NPs respectively. The entrapment efficiency was 93.34 ± 0.40 for CUR-NPs, and 98.46 ± 0.06 for CUR.SA-NPs. Physical and structural characteristics of the formulated nanoparticles were investigated using FTIR, NMR, XRD, SEM, and TGA and each attest to the formation of the functionalized CUR.SA-CMNPs. In vitro drug release illustrated a sustained release profile of CUR and CUR.SA over a period of 3 days and an excellent cytotoxicity and intracellular uptake by CRC cell lines (SW480 and HCT116). Thus, CUR-NPs and CUR.SA-NPs can be considered as a promising delivery strategy for CRC treatment.