MECHANISM OF DOXORUBICIN RELEASE FROM POLYMERIC PARTICLES - AN INTERFACIAL TRANSFER LIMITED PROCESS AFFECTED BY SERUM-PROTEINS

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 b ovine serum albumin or esterases decrease this energy barrier by cover ing the particle and changing the surface properties, In parallel, the evolution of the carrier's radius was followed by light-scattering ex periments, No significant alteration of the particles was observed at the time of the release either in the presence or in the absence of pr oteins; this confirms the idea of a surface-controlled process, The im portance of the surface state as a tool for the regulation of the rele ase is discussed. (C) 1996 Academic Press, Inc.