In vitro study on N-succinyl chitosan and chitosan (control) matrices for selective colon delivery of 5-aminosalicylic acid is described. Matrices containing β-cyclodextrin were also prepared. As shown by DSC analyses, the drug was successfully loaded into the matrices reaching up to 95% entrapment efficiency. Swelling and drug release were studied at pH 1.2, pH 7.4, and in a pH gradient medium to simulate the gastro-intestinal transit. Main result of this study was a higher capability of N-succinyl chitosan alone to better control drug release in the simulated gastro-intestinal transit: N-succinyl chitosan gave the lowest release in acid medium (≅15%) and the highest in alkaline environment (≅92%). The cyclodextrin did not provide any interesting role since they enhanced drug release from the unswollen N-succinyl chitosan (pH 1.2, ≅50% drug release). Kinetic studies showed a non-Fickian transport from all the matrices, which also showed good mucoadhesive properties (work of adhesion ≅1.5 mN mm).