Nanoparticles loaded with 5-fluorouracil (5-FU) for colon cancer therapies were prepared using the solvent evaporation technique, which involved lyophilization by freeze-drying. Formulations produced a substantially high encapsulation efficiency of approximately 93%. A positive correlation was seen when increasing polycaprolactone (PCL) and/or PVA concentrations and the size of nanoparticles produced. Increasing PCL concentration had a considerable influence on PDI while increasing PVA concentration had a lesser effect. All nanoparticles possessed a negative zeta potential, particularly in formulations with low polymer and polymer emulsifier concentrations. The formulation with the lowest PCL and PVA concentration was characterized by the most optimal properties; which accounts for the desirable delayed release profile of the active drug in dissolution testing indicating an improved targeting capability and enhanced bioavailability at the action site. Cytotoxicity studies showed that 5-FU loaded PCL nanoparticles had higher antiproliferative effect than free 5-FU on Caco-2 cell line (p < 0.05). The encouraging results obtained offer reasons for optimism regarding the future of 5-FU nanoparticles as a promising drug delivery system which could be further improved by including either enteric coating or encapsulating the nanoparticles onto microparticles to overcome unanticipated degradation.
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