The development of a novel oral 5-Fluorouracil in-situ gelling nanosuspension to potentiate the anticancer activity against colorectal cancer cells

Abstract

5-Fluorouracil is an anticancer drug with a short biological half-life. This study aimed to develop oral sustained-release nano-formulations of 5-Fluorouracil. 5-Fluorouracil-carrageenan coated particles were prepared and characterized. To formulate a suspension, the coated particles were encapsulated in an aqueous hydrodynamic gel of sodium alginate with carrageenan-lambda or chitosan in excess, and the optimum suspension was determined using drug release analysis, gel characterization, and particle size analysis. Afterward, the optimal formulation was tested against colorectal cancer cells to assess the cell viability, level of apoptosis, and caspase-9 activity. Interestingly, the sustained-release formulations with the best ability to form a coherent insoluble sedimented gel when in contact with 0.1 N hydrogen chloride were the F5 and F6 formulations. Moreover, those formulations were nanosuspensions (20–63 nm) and the 5-Fluorouracil nanoparticles released from them were coated with carrageenan and sodium alginate. After the antitumor characterization against HCT-116 cells, the 5-Fluorouracil nanoparticle formulation was approved for its contribution to the sustained-release characteristics, sensitivity, and time-dependent efficacy. This nanosuspension is suggested to serve as a long-acting therapy, which it could protect the drug nanoparticles through the pH-selective and sustained release matrix, in-situ gel formation in the stomach, and the polymer coating of the released nano-drug particles.