In order to complement the promising in vitro results, the purpose of this study was to test, in vivo in a suitable efficacy model, the performance of the two innovative formulations, i.e., the Na-DOC gel containing 0.05% w/w CP and the nanoparticle suspension in chitosan gel (NP) containing 0.005% w/w CP. A commercial cream containing CP 0.05% w/w was used for comparison purposes. In vivo pharmacodynamic activity was evaluated using the carrageenan-induced hind paw edema test on rats . The effect of formulations on the barrier properties of the stratum corneum was determined using TEWL; histological analysis was performed to evaluate the possible induction of morphological changes.