Ketoconazole (KTZ) is a widely used antifungal drug. Despite its broad spectrum as antifungal agent, it suffers from two characteristics that make difficult its utilization. It is poorly water soluble and undergoes very easily chemical degradation, such as oxidation and hydrolysis. The paper reports a new system based on solid lipid nanoparticles (SLN) entrapped into polysaccharidic hydrogels to be employed as modified delivery system of ketoconazole in topical formulations. Three different lipid phases (compritol, precirol and a mixture precirol/almond oil) were employed to prepare SLN and all the nanoparticles were characterized for their mean particle diameter, polidispersion index and zeta potential. All the systems were able to efficiently encapsulate the drug (entrapment efficiency > 90%). SLN formulations were able to protect the drug from UV degradation, even if partially. The incorporation of KTZ-loaded SLN into dextran hydrogels allowed the preparation of systems having rheological characteristics suitable for different topical applications. The efficacy of the system has been exploited testing the antifungal activity against Candida albicans, whereas the skin tolerability of all the preparation components was tested on rabbits.