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

Abstract

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.

Latest Trends in Surface Modification for Dental Implantology: Innovative Developments and Analytical Applications

“…The elution time of the active molecule is also affected by surface topographies of the implants and the drug load. Biomaterials such as polymeric matrices, hydrogels and nanoporous matrices have been evaluated for this purpose [179][180][181][182][183][184][185]. Types of carrier-based drug delivery biomaterials have included dendrimers and micro-and/or nanoparticles (e.g., micro-and nanospheres, nanofibers and nanocapsules) [186].…”

Customized Therapeutic Surface Coatings for Dental Implants

“…The elution time period of the drug molecule strictly depends upon the technical topographies integrated in implant coatings and the drug load. A range of nanomaterials including polymeric systems [76,77], hydrogel-based models [78][79][80], and nanoporous materials [81,82] have been explored for the manufacturing of drug-eluting dental implants. A novel drug delivery model should ensure drug safeguard from a hostile environment, plausible controlled release (in response to environmental stimuli like temperature or pH), and selectivity of a drug to specific organs, cells, or tissues in order to show improved pharmacodynamic parameters of the drug [83,84].…”

“…Kamath et al showed that diffusion or dissolution characteristics of drug molecules affect their release kinetics [89]. Drug release, if governed by the pure diffusion mechanism, is very quick due to the high in vivo clearance [78,79]. To attenuate the diffusional drug release of molecules, biorthogonal strategies were introduced to develop an affinity bond between the polymeric network and peptide (an affinity-based approach) that covalently links a small protein receptor and the observed tunable release rates [90].…”

On the ability of chromatographic mass balance to predict solute diffusivity in drug delivery systems

“…In previous works we hypothesized that the ability of drug molecules to aggregate in dimers and trimers influences their behavior in term of drug delivery from hydrogel and it is different respect to what is happening in aqueous solutions. 37 Schematization present in Figure 2 represents the main phenomena: respect to the previous case (nonaggregative drug) the main difference is that here also the role of aggregation should be taken into account. In particular hydrogel network sequestrate drug monomers (adsorbing into the pores) that are not still available for aggregation.…”