The clinical use of ketoconazole has been related to some adverse effects in healthy adults, specially local reactions, such as severe irritation, pruritus and stinging. The purpose of the present work is the assessment of ketoconazole stability in aqueous SLN and NLC dispersions, as well as the physicochemical stability of these lipid nanoparticles, which might be useful for targeting this drug into topical route, minimizing the adverse side effects and providing a controlled release. Lipid particles were prepared using Compritol 888 ATO as solid lipid. The natural antioxidant alpha-tocopherol was selected as liquid lipid compound for the preparation of NLC. Ketoconazole loading capacity was identical for both SLN and NLC systems (5% of particle mass). SLN were physically stable as suspensions during 3 months of storage, but the SLN matrix was not able to protect the chemically labile ketoconazole against degradation under light exposure. In contrast, the NLC were able to stabilize the drug, but the aqueous NLC dispersion showed size increase during storage. Potential topical formulations are light-protected packaged SLN or NLC physically stabilized in a gel formulation.