Investigation of the Swelling Response and Loading of Ionic Microgels with Drugs and Proteins: The Dependence on Cross-Link Density

The pH and NaCl induced swelling response and drug and protein loading of poly(methacrylic acid-co-acrylic acid) microgels (4-10 μm diameter) were measured as a function of cross-link density. The swelling ratio (Q) of the microgels increased linearly from 2 to 12 when the mole fraction of crosslinking monomer decreased from 0.25 to 0.10 (at pH’s > 5.3). In the presence of 5 M NaCl (at pH’s > 5.3), microgels with cross-linking feed ratios of 0.25 and 0.10 swelled to only 80% and 60% of their maximum volume measured at low ionic strength, respectively. To determine the average pore size in the different cross-linking density microgels (feed ratios ) 0.25, 0.20, 0.15, and 0.10), we measured the size cutoffs for the uptake of different sized proteins. On the basis of these size exclusion experiments, we calculated the number of monomers between cross-links in each of these gels to be 6.5, 9.5, 12.5, and 16.5, respectively. These values were used in our theoretical modeling of the network swelling (modified Flory-Huggins thermodynamic model) to predict the pH-Q dependence for different degrees of cross-linking. The model predictions of the microgel pH swelling response as a function of cross-link density were in good quantitative agreement with experiments. Experimentally, the loading of smaller drug molecules did not have clear molecular weight dependence for the different cross-link density microgels. However, differences in the loading behavior of these molecules on the basis of their partition coefficients indicated that binding affinity, molecular packing, and condensation were important factors that need to be explored to optimize microgels for use in specific drug delivery applications.