Abstract
5-fluorouracil (FU) is an anticancer treatment with disadvantages of a short half-life and the need for multiple intravenous administrations. The idea was to formulate oral sustained-release nanosuspensions of FU, which was utilizing drug-soy protein (Sp) solid dispersions, protein-polysaccharide gels, and sedimentation of insoluble gel formulations for the development of colon resident dosage form. Sp-FU and Sp-Carrageenan kappa-FU solid dispersions were prepared and characterized. Furthermore, the solid dispersions were suspended in the aqueous gel-forming vehicle of sodium alginate (NA) with Sp excess. The nanosuspensions were characterized using UV-spectroscopy, zeta-sizer, particle size analyzer, scanning electron microscopy, and antitumor evaluation against HCT-116 cancer cells. The optimum formulations with insoluble gel of good strength, coherence, and resilience in contact with simulated gastric media were two formulations. The overall pH-profile release percentages of the optimum formulations were less than FU alone by more than 48% of the drug amount. Furthermore, those optimum formulations were nano-drug formulations. The FU nanoparticles were approved to be released as coated particles with NA. After the in vitro cell-line evaluation against colorectal cancer, the sustained-release behavior, nanoparticle formation, and the association of NA and Sp, could enhance the time-dependent efficacy compared to the free drug. Furthermore, this Sp containing nanosuspension may be an effective and safe oral alternative for cancer chemotherapy due to the need for a lower FU dose using FU nanoparticles to induce a similar effect to the original free FU (macro-sized drug).
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