Long-Term Release of Large Biologics Via High-Affinity Supramolecular Polymeric Hydrogels

Monoclonal antibodies (mAbs) have emerged as a major class of therapeutic agents due to their high specificity, sensibility, and much-reduced side effects. Despite these advantages, significant challenges remain in maintaining a therapeutic dose in the body for an extended period. Developing biocompatible materials that can release specific therapeutic antibodies at a controlled rate is highly sought after in drug delivery. Peptide-based hydrogels have garnered growing interest as effective drug delivery systems for their tunability, biodegradability, and biocompatibility. mAbs can be easily incorporated into the hydrogel matrix and released at a rate that depends on the hydrogel swelling (physical disintegration), chemical degradation, and their binding affinity to the hydrogel networks. Our lab has developed a class of supramolecular hydrogels using a protein A mimicking peptide that demonstrates a high binding affinity to mAbs. Previous work has shown that the antibody release from these hydrogels can be tuned based on the ligand density and the initial ligand loading ratio relative to the delivered proteins. My research focuses on hydrogel mesh size as another potential variable for further optimizing these hydrogels to model the release profile of current mAb-based therapeutics. The goal is to extend the duration of their therapeutic effect and reduce the frequency of injections. My recent findings suggest that the linker chemistry that bridges the mAb-binding ligand to the immunofiber has an important impact on the release profile of mAb, with longer linkers resulting in a more linear release profile. Given that the length of the linker also affects the hydrogel mesh size, we speculate the smaller mesh size as a result of employing a longer linker would have a smaller confinement ratio, thus limiting the mAb diffusion and extending their release period. By varying the mesh size and mAb diffusion mechanics, I envision that these hydrogels can be eventually optimized for controlled mAb release, enabling sustained therapeutic levels and enhancing the overall patient experience.