(182l) Supramolecular Hydrogels: Complex Rheological Behavior of Polymer-Nanoparticle Hydrogels and Its Impact on Drug Release Kinetics

Supramolecular hydrogels are appealing for biological applications such as drug delivery, 3D printing bio-inks, and cell therapies. These applications create a diverse set of material requirements which are met by exploiting the broad tunability of the hydrogel’s material properties through modifications to the composition, crosslinking moieties, concentration, and molecular weight. The effects of these variables on the material properties can be complex and difficult to characterize. In addition, the quantity of formulation knobs to alter creates a design space that is vast and difficult to rationally navigate.

Herein we present the complex rheological and diffusive behavior for supramolecular polymer-nanoparticle hydrogels, comprising hydroxypropyl methylcellulose and poly(ethylene glycol)-b-poly(lactic acid) nanoparticles, from the perspective of designing an injectable controlled release drug-delivery platform. The hydrogel’s associative gel formation dynamics and the strong non-Newtonian rheological behavior, including yield stress fluid behavior and shear-thinning, are presented as a function of variations in the formulation of the polymer-nanoparticle hydrogels. Diffusion, measured by fluorescence recovery after photobleaching (FRAP), is presented to demonstrate the correlation between the mechanical properties of the hydrogels and the transport within the hydrogel. It is shown that formulations created to expand the timescale of release may result in an inadvertent effect of increasing the viscosity and yield stress of the hydrogels, precluding injectability. We also present a design-oriented approach, developed from our systematic rheological and diffusive characterization, which allows for visualizing the effects of each formulation knob on intrinsic material properties and behavior. Furthermore, this approach allows for the generalization of the hydrogel platform and provides a means for engineering formulations for a more diverse set of applications beyond injectable therapeutics.