(662c) Ionically Crosslinked Polymer Networks for the Multiple-Month Release of Small Molecules

Self-assembled hydrogels are widely studied as materials for sustained release applications. Yet, unless their payloads are able to bind or bond to the network, or are loaded into colloids (e.g., nanoparticles or liposomes) that are dispersed within the gels to moderate the release rates, most self-assembled hydrogels are too permeable to deliver small hydrophilic molecules over long (multiple-week or month) times. Here, we report on how gel-like coacervates, which self-assemble via ionotropic gelation of poly(allylamine hydrochloride) (PAH) with either pyrophosphate (PPi) or tripolyphosphate (TPP), can be used to address this limitation. Rheological analysis of these gel-like networks reveals them to have very high (G'_â?? > 10^5 Pa) plateau moduli, which are indicative of small (nanometer-scale) hydrodynamic mesh sizes. These small mesh sizes make PAH/PPi and PAH/TPP complexes effective barriers to solute diffusion, and enable them to sustain small hydrophilic molecule release over many months. Isothermal titration calorimetry (ITC) analysis shows that this highly-sustained release occurs even without payload/network binding, which confirms that the slow release is primarily caused by the small mesh size (and not payload-specific binding interactions). The release rates achieved with these materials can also be easily tuned by varying the encapsulated payload content and gel thickness. This ability to obtain tunable release regardless of the payload/network binding suggests that PAH/PPi and PAH/TPP networks can serve as simple sustained release platforms for a wide range of small molecules.