Mean-field modeling of the encapsulation of weakly acidic molecules in polyelectrolyte dendrimers

The unique architecture of dendrimers has attracted interest in a wide variety of biomedical applications such as drug delivery. In order to gain insight into the solubilization of drugs inside dendrimer architectures, we have developed and numerically implemented a self-consistent field theory model for the equilibrium characteristics of charged dendrimer molecules in the presence of weakly acidic drug molecules. Using such a model, we examine the relative influence of excluded volume, electrostatic, and local enthalpic interactions upon the solubilization of drugs in dendrimers. When only excluded volume interactions are accounted, there is no driving force for drug solubilization inside the dendrimer, and hence depletion of the drug from the dendrimer molecule (relative to the bulk drug concentration) is observed. The inclusion of electrostatic interactions within the model results in solubilization of drugs within the dendrimer. The solubilization of the drugs is shown to increase with increasing drug charge density and increasing dendrimer generation number. We probe the effect of enthalpic interactions and demonstrate that the number of drug molecules encapsulated through enthalpic interaction is dependent upon the number of dendrimer monomers, the enthalpic interaction parameters between the dendrimer and drug (χPD), and the drug and solvent (χDS). We also analyze the combined effects of the preceding interactions to identify the synergism in their influence and delineate the relative importance of different parameters such as pOH, size of the drugs, and the Bjerrum length of the solution in influencing the encapsulation of drugs by dendrimer molecules.