Self-diffusion of water and poly(amidoamine) dendrimers in dilute aqueous solutions

Abstract

Medium generation PAMAM dendrimers are extensively researched as drug delivery vehicles therefore detailed knowledge of their physico-chemical properties in solution is vital. We have selected ethylenediamine core, generation five poly(amidoamine) (PAMAM_E5) dendrimers (amine terminated PAMAM_E5.NH₂ and its succinamic acid derivative PAMAM_E5.SAH, respectively) as model compounds to study their dynamic behavior in water as a function of pH and concentration. Diffusion coefficients of water and the dendrimers were determined in deuterium oxide using pulse-field gradient stimulated echo (PGSE) NMR. The diffusion rate for PAMAM_E5.NH₂ increased monotonously with increasing pH values while for PAMAM_E5.SAH a maximum was found at an isoelectric value of pH = 5.7. The apparent diffusion coefficients of dendrimers decreased linearly with increasing concentration measured at their self-pH (pH = 9.4 for PAMAM_E5.NH₂ and pH = 5.7 for PAMAM_E5.SAH) in the absence of added salts. The observations could be explained by considering hard sphere interactions between strongly hydrated dendrimer molecules. The average hydrodynamic radii of dendrimers were determined by extrapolating the measured diffusion coefficients to zero dendrimer concentration and applying the Stokes–Einstein equation. The calculated values were R_H = 3.05 ± 0.04 nm for PAMAM_E5.NH₂ and R_H = 3.37 ± 0.08 nm for PAMAM_E5.SAH respectively. Measured diffusion coefficients of water (D₂O) also decreased linearly with increasing dendrimer concentration. From the concentration dependence, the average number of water molecules that form one dynamic unit with one macromolecule could be calculated on the basis of three different obstruction models. It has been concluded that hydrated PAMAM dendrimers in aqueous solutions behave as soft colloids against solvent molecules but as hard-sphere colloids against each other. Their equivalent hard-sphere radii were found to be equal to the measured hydrodynamic radii.