The design and in vitro release characterization of human cross-linked haemoglobin microcapsules containing doxorubicin for potential chemoembolization use

Cross-linked human haemoglobin microcapsules were prepared by reacting native haemoglobin with terephthaloy1 chloride using an interfacial polymerizatian process. Low cross-1inking agent concentration, and short time reaction produced weakly cross-linked microcapsules which incorporated 707. of the doxorubicin by adsorption from aqueous solution. Only small amounts of doxorubicin were released from the microcapsules in distilled water over 24 hours. However, the presence of electolytes in the aqueous sink solution altered profoundly the release profile of doxorubicin and significantly increased the release rate of the drug. These results suggest that there was a competitive fixation of the cation on the binding sites, identified as carboxyl groups available to the drug molecules. Release profile of doxorubicin from the microcapsules was analyzed according to kinetic models using the nonlinear regression search procedure. Doxorubicin release from the microcapsules was found to be controlled by an ion-exchange particle diffusion process. This was confirmed by the “interruption test” which is considered the best technique for distinguishing between particle and film diffusion controlled kinetic process.