Sorafenib and 5-Fluorouracil Loaded Dual Drug Nanodelivery Systems for Hepatocellular Carcinoma and Colorectal Adenocarcinoma

Abstract Purpose: Here, we reported the sysnthesis of two clinically used drugs, 5-fluorouracil (5FU) and Sorafenib (SF)-loaded in chitosan nanoparticles and their priliminary study of therapeutics effect on hepatocellular carcinoma and colorectal adenocarcinoma cell lines. We have formulated chitosan nanoparticles (CS NPs) loaded dual (SF and 5-FU) drugs nanodelivery system for SF/5FU-CS NPs and their coating version with folic acid (FA) for SF/5FU-CS-FA NPS. Human hepatocellular carcinoma (HepG2) and colorectal adenocarcinoma (HT29) cell lines were selected for in vitro cytotoxicity studies to evaluate the preliminary anticancer efficacy of both nanoparticles.Characterization: The physiochemical characterization of SF/5FU-CS NPs and SF/5FU-CS-FA NPs were investigated by DLS, FESEM, HRTEM, EDX, XRD, TGA, FTIR, and HPLC methods.Results: DLS study has shown the size of SF/5FU-CS and SF/5FU-CS-FA nanoparticles were about 78±14 nm and 142±25 nm, respectively. HRTEM and FESEM studies confirmed the spherical shape with size of 60-70nm for SF/5FU-CS and 90-150 nm for SF/5FU-CS-FA NPs. The XRD results indicated the drug loading and folate-coating comfirmation. FTIR peaks confirmed the presence of drugs in the nanoparticles, as well as folate-coating on the surface of the nanoparticles. TGA results demonstrated the thermostability of both nanoparticles. The release profiles of SF and 5FU from the two designed NPs were found to be in a sustained manner according to the pseudo-second-order kinetics model indicating a good delivery system for tumor cells. The cytotoxicity studies confirmed the better anti-cancer activity of the nanoparticles compared to the free 5-fluorouracil and sorafenib against liver cancer cells, HepG2 and colon cancer cells, HT29. Conversely, both NPs were found not toxic towards normal human dermal fibroblast cells (HDF) cells.