Effect of thymoquinone-loaded lipid–polymer nanoparticles as an oral delivery system on anticancer efficiency of doxorubicin

In this study, thymoquinone (TQ) was encapsulated into lipid–polymer nanoparticles (LPNPs) consisting of phosphatidylcholine (PC) and poly lactide–co-glycolide (PLGA) to enhance anticancer and oral delivery efficiency of TQ. We also co-delivered TQ nanoparticles with free doxorubicin (DOX) to increase DOX efficiency. Single emulsion solvent evaporation method was exploited to prepare PLGA-TQ and PLGA-PC-TQ NPs. The physicochemical properties of synthetized NPs and their cellular uptake across Caco-2 cells were assessed. Cytotoxicity of different formulations of TQ and their co-delivery with free DOX were determined by MTT assay on colon cancer cell lines (C26). Cell migration was also evaluated by wound healing migration assay. LPNPs containing TQ with an average diameter of 184 nm and 60% loading efficiency showed more release at simulated intestinal fluid pH of 6.8 compared to polymeric NPs. At an acidic pH, however, the release of TQ from PLGA-PC was about 2% after 120 h. The cytotoxicity studies indicated that PLGA-PC-TQ NPs improved anticancer activity of DOX more than TQ NPs. Uptake of PLGA-PC-TQ through the Caco-2 cells was 2.5 times greater compared to NPs without PC. PLGA-PC-TQ NPs also exhibited significantly greater reduction of cancer cell migration. The results demonstrate that co-delivery of PLGA-PC encapsulated TQ through oral administration and free DOX could improve anticancer efficiency of DOX.