Project Summary: For the international and Saudi market, the development of safe, targeted, and effective oral alternatives to the 5-Flourouracil (5-FU) injections in colorectal cancer management is highly needed to elicit the patients' convenience, compliance and adherence to the treatments. The novel products may reduce hospitalization costs in comparison to the 5-FU injections. The first objective will be the development and optimization of different platforms to encapsulate the 5-FU and anti-inflammatory agents in oral-targeted nanosystems. The nanosystems will be tested for the conjugation nature of 5- FU/anti-inflammatory agents, the gelling ability in the simulated gastro-intestinal media, the passive and active targeting abilities toward the colonic area, sustained-release of 5-FU, and the chemical and morphology of the nanosystems. Furthermore, efficacy and selectivity for the optimized systems will be elucidated using a suitable cell-line model after exposure to the optimized systems, 5-FU injections and control to assess the cytotoxicity and gene expression levels for the genes encoding for the 5-FU uptake proteins, oncogenes, tumour suppressor genes and pro-inflammatory markers. Finally, the optimized systems will be given for suitable animal models, such as rats. After all, the safety will be elucidated using the 5-FU absorption analysis for the in vivo animal model.