The release of the anticancer drug doxorubicin from particles made of polyisohexylcyanoacrylate has been studied to understand the behavior of this colloidal system under biological conditions, Kinetic analyses, performed using fluorescence spectroscopy, have evidenced a process dominated by the interfacial transfer of the drug from the polymer to the aqueous phase, This transfer occurs with a 35 kcal/mol activation energy in a protein-free medium, We have shown that proteins such as bovine serum albumin or esterases decrease this energy barrier by covering the particle and changing the surface properties, In parallel, the evolution of the carrier’s radius was followed by light-scattering experiments, No significant alteration of the particles was observed at the time of the release either in the presence or in the absence of proteins; this confirms the idea of a surface-controlled process, The importance of the surface state as a tool for the regulation of the release is discussed.