Binding mechanism of doxorubicin in ion-exchange albumin microcapsules.

The absorption efficiency of cross-linked albumin microcapsules was evaluated as a function of various experimental conditions in an attempt to elucidate the doxorubicin binding mechanism of these microcapsules. The amount of drug absorbed augmented with increasing doxorubicin concentration until saturation was reached. Neither a Langmuir nor a Freundlich isotherm relationship was observed, indicating that the fixation of doxorubicin on the microcapsule walls did not follow a common physical adsorption process. Decreasing the mean particle diameter of the microcapsules increased the absorption rate and the total amount of doxorubicin absorbed, as expected. The absorption rate was enhanced by the elevation of the stirring rate of the aqueous drug solution. Furthermore, the presence of electrolytes in this aqueous solution profoundly altered the absorption profile of doxorubicin. Increasing the NaCl concentration in the solution reduced the total amount of drug absorbed. Moreover, the nature of the cation used also affected the absorption profile. These results suggested that there is a competitive fixation of the cation on the binding sites (identified as R-COO groups) available to the drug molecules. The weakly cross-linked microcapsules acted as cation-exchange resins which can exchange their labile sodium with the protonated drug present in the solution. This was also confirmed by the results of the titrimetric assay of the acidic microcapsules with NaOH.