The purpose of this research was to formulate nanocomposites comprising of celecoxib with shellac and eudragit S100 for solubility enhancement and targeting drug delivery to the colon. Celecoxib belongs to the class NSAIDs and it shows anticancer activity as well, by COX-II dependent and independent mechanisms. The nanocomposites were prepared by the microwave-assisted method. The prepared nanocomposites were evaluated by techniques such as FTIR, DSC, XRD, solubility determination studies, in-vitro dissolution studies, SEM and TEM. The effect of the drug and polymer ratio on the solubility and the release of celecoxib at colonic pH were evaluated. The solubility of the drug increases up to a certain level when the polymer concentration increases, after which it was found to be decreased. The solubility studies revealed that as the concentration of the polymer increases up to the optimum level, the solubility of the drug increases. Enhancement of solubility for optimum batches was found to be 26.22 and 8.58 μg/ml for a 1:3 ratio of celecoxib-shellac nanocomposite (CSNC) and 1:4 for celecoxib-eudragit nanocomposite (CENC), respectively, as compared to pure celecoxib. SEM and TEM analysis showed the surface texture of the composite and the size of nanoparticles embedded in the polymeric matrix. Needle-shaped nanoparticles were observed with a size of about 50 nm in the polymeric matrix. The optimum ratio of drug to polymer showed the release of drug by 92.72 ± 1.7% and 79.66 ± 2.4% for CSNC and CENC, respectively, at the end of 8 h at colonic pH.