The Role of Drug–Drug Interactions in Hydrogel Delivery Systems: Experimental and Model Study

To address the increasing need for improved tissue substitutes, tissue engineering seeks to create synthetic, three‐dimensional scaffolds made from polymeric materials able to incorporate cells and drugs. The interpretation of transport phenomena is a key step, but comprehensive theoretical data is still missing and many issues related to these systems are still unsolved. In particular, the contribution of solute–solute interactions is not yet completely understood. Here, we investigate a promising agar–carbomer (AC) hydrogel loaded with sodium fluorescein (SF), a commonly used drug mimetic. The self‐diffusion coefficient of SF in AC formulations was measured by using high resolution magic angle spinning NMR spectroscopy (HR‐MAS NMR). Starting from experimental data, a complete overview on SF transport properties is provided, in particular a mathematical model that describes and rationalizes the differences between gel and water environments is developed and presented. The hydrogel molecular environment is able to prevent SF aggregation, owing to the adsorption mechanism that reduces the number of monomers available for oligomer formation at low solute concentration. Then, when all adsorption sites are saturated free SF molecules are able to aggregate and form oligomers. The model predictions satisfactorily match with experimental data obtained in water and the gel environment, thus indicating that the model presented here, despite its simplicity, is able to describe the key phenomena governing device behavior and could be used to rationalize experimental activity.