The release of fluorescein from polyethylcyanoacrylate (PECA) or polyisobutyl-cyanoacrylate (PICA) nanoparticles was affected by the surfactants used for the preparation. The different surfactants also modified the molecular weight, size and loading of the nanoparticles. However, these factors were not be responsible for the different release. According to the release profiles and the Baker-Lonsdale model, a portion of fluorescein was concentrated near the nanoparticle surface. Thus, a non-homogeneous distribution of the fluorescent probe inside the nanoparticles was hypothesized. This distribution could reflect the fluorescein position inside the micella during the polymerization stage, or could be reached during the washing stage as the consequence of a different effect of the surfactants on the porosity of the nanoparticle structure.