Methotrexate (MTX), is a potent immunomodulating drug and widely used in the treatment of cancer, psoriasis and others disease. Despite its efficacy, the use of MTX is greatly limited due to its toxicity. To solve this problem, we prepared nanoparticles of tetraethyl orthosilicate (NP-TEOS) containing the compound methotrexate (MTX), by the sol-gel method. This drug delivery system (DDS) showed a loading efficiency of 39.7%. Size distribution studies were performed with dynamic light scattering and scanning electron microscopy revealing that these particles were spherical in shape, with a mean diameter between 140-430 nm and a low polydispersity (0.12 – 0.26). Also the particles displayed a low tendency toward aggregation which was confirmed by the low zeta potential -61.4 mV. Profile release showed a slow release loaded with MTX (PBS buffer pH = 7.4). The slow release can be attributed to the low porosity of the NP-TEOS and the extremely low diffusivity of MTX in aqueous media. B16-F10 cells were used to assay the toxicity and uptake of NP-TEOS showing to be nontoxic without MTX making a good candidate for DDS.