A rotatable central composite design was applied to the formulation of poly(butyl 2-cyanoacrylate) nanoparticles with the aim of modifying some physico-chemical properties of these carriers in a controlled way. The joint effect of stabilizer concentration and monomer concentration on the mean particle size, on the electrophoretic mobility and on the polymer molecular weight has been investigated. The results demonstrate that the particle size is only dependent on the stabilizer concentration, nevertheless the electrophoretic mobility and the molecular weight distribution were affected simultaneously by the monomer and the stabilizer concentrations. Moreover, using the response surface diagrams it is possible to deduce the experimental conditions to design particles with the desired properties. Finally, the degradation rates for two different molecular weight formulations were compared, showing the relevance of this property.