Based on statistical analyses of death, colorectal cancer was the fourth most fatal cancer in the world. Targeting the medicine to the specific area of the colon is the main problem in the treatment of colorectal cancer. The development of PLGA-based nanoparticles to target and maintain medication release at the colon for the successful treatment of colorectal cancer was the primary goal of the current study. While PLGA's role is to maintain medication release due to its mucoadhesion property, Eudragit S100's purpose was to stop drug release in the stomach and small intestine. Modified nanoprecipitation was used to create the nanoparticles, and the MTT assay was used to test for cytotoxicity. According to the results of the cytotoxicity investigation, Capecitabine-loaded PLGA-based nanoparticles were more effective at inhibiting HT 29 cell lines than the pure medication did at all concentrations (10 to 0.0001). The outcomes of the in vitro investigation were validated by the pharmacokinetic (PK) study for the aqueous solution of Capecitabine and the optimised formulation. The area under the curve (AUC) for the formulation containing nanoparticles was discovered to be twice as high as that for the pure medication, demonstrating improved bioavailability. For more effective therapy of colorectal cancer, the colon can be more effectively targeted with PLGA-based nanoparticles