Abstract

“Supramolecular biomaterials exploit rationally-designed non-covalent interactions to enable innovative approaches to drug formulation and delivery. For example, supramolecular interactions can be used to dynamically cross-linking polymer networks, yielding shear-thinning and self-healing hydrogels that allow for minimally invasive implantation in vivo though direct injection or catheter delivery to tissues. Alternatively, rationally designed high-affinity interactions can be used to non-covalently modify therapeutic proteins, endowing them with prosthetic function such as enhanced stability in formulation or extended activity in vivo. Herein, we discuss the preparation and application of shear-thinning, injectable hydrogels driven by dynamic non-covalent interactions between modified biopolymers (BPs) and biodegradable nanoparticles (NPs) comprised of poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA). Owing to the non-covalent interactions between PEG -b-PLA NPs and BPs, the hydrogels flow under applied stress and their mechanical properties recover completely within seconds when the stress is relaxed, demonstrating the shear-thinning and injectable nature of the material. Moreover, the hierarchical construction of these biphasic hydrogels allows for multiple therapeutic compounds to be entrapped simultaneously and delivered either co-delivered or delivered independently of one another in a user-defined manner with release profiles that are tunable over several months. These materials open new opportunities to address fundamental biological questions in immunotherapy as well as to enable passive immunity strategies and long-term treatment of a variety of chronic disease targets. Further, we will discuss the use of supramolecular interactions to append functionality to therapeutic proteins for applications in formulation and therapy. This non-covalent approach to modification of authentic proteins is highly modular and allows for formulation of historically incompatible proteins. Overall, this presentation will demonstrate the utility of a supramolecular approach to the design of biomaterials affording unique opportunities in the formulation and controlled release of therapeutics.