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This survey was conducted to fabrication of PLGA-based nanosystems modified with PEG, chitosan and folic acid to delivery colchicine to cancer cells and to investigate its antioxidant and pro-apoptotic effects. The dual emulsion-evaporation solvent method was used for loading of colchicine on PEGylated PLGA nanoparticles (COL-PP-NPs) and after surface modification with chitosan and folic acid (COL-PPCF-NPs), the nanoparticles were characterized by DLS, SEM and FTIR methods. The HPLC procedure was used to assess the amount of FA binding and COL loading. Antioxidant capacity (ABTS and DPPH free radical scavenging) and toxicity (MTT) of COL-PPCF-NPs were evaluated and then cell inhibition mechanism was assessed by AO/PI staining, flow cytometry and qPCR assay. COL-PPCF-NPs with a size of 250 nm were synthesized in a stable (zeta potential: +34 mV) and mono-dispersed (PDI: 0.32) manner. FA binding and COL loading were reported to be 55% and 89.5%, respectively. COL-PPCF-NPs showed antioxidant effects by inhibiting the free radicals ABTS (108.07 µg/ml) and DPPH (361.61 µg/ml). The selective toxicity of COL-PPCF-NPs against HT-29 cancer cells (118.5 µg/ml) compared to HFF cells was confirmed by MTT data. Increased apoptotic cells (red color) in AO/PI staining, cell arrest in phase SubG1 and G2-M, and altered expression of apoptosis genes confirmed the occurrence of apoptosis in HT-29 treated cells. The use of PPCF-NPs system for delivery of COL can lead to selective toxicity against cancer cells and induction of apoptosis in these cells by folate-mediated binding mechanism at folate receptor positive HT-29 cancer cells.

Nanofabrication of PLGA-PEG-chitosan-folic acid systems for delivery of colchicine to HT-29 cancer cells