(162o) Injectable Drug Eluting Nanodroplet (DEN) Hydrogels for Controlled Delivery

Hydrogels are an attractive class of materials for drug delivery due to their highly biocompatible nature. However, drug release kinetics are often tuned at the expense of hydrogel mechanical properties, which can significantly limit the applicability of a system. Here, we demonstrate a fully-tunable and injectable hydrogel system composed of an engineered recombinant protein physically crosslinked with drug-loaded and chemically-stabilized multilamellar lipid vesicles, termed drug-eluting nanodroplets (DENs). These DENs are surface-functionalized with a peptide sequence that participates in gelation-inducing self-assembly with the recombinant protein, with mechanical properties controlled by the extent of DEN-functionalization. This gel is shear thinning and self-healing, allowing for injectability and form-fitting of the gel into irregular cavities. The release rate is dependent on, and tuned by, the chemical stabilization of the DENs, thus avoiding alteration of gel mesh size and mechanics. Using the DENs as the drug carrier also provides protection to otherwise quickly degraded drugs that have limited clinical application using conventional bolus delivery. Additionally, the system is made up of enzymatically degradable components, thus can be biodegraded and resorbed and not require surgical removal.