Expanding Hydrogel Platforms for the Encapsulation and Sustained Release of Hydrophobic Therapeutics

• Jillian Lybeck-Brown, Chemical Engineering, University of Delaware

• April Kloxin, Chemical and Biomolecular Engineering, Materials Science and Engineering, University of Delaware

Polyethylene glycol (PEG)‐based hydrogels are promising materials for drug delivery due to their biocompatibility and tunable material properties, which enable control over cargo release. Water-soluble cargoes can be easily incorporated into the aqueous precursor solutions used to synthesize the gels. In turn, these gels are particularly well-suited for the diffusion-controlled delivery of hydrophilic therapeutics. However, approximately 40% of approved drugs and nearly 90% of drug candidates are hydrophobic, illustrating the critical need for improved delivery platforms for poorly water-soluble compounds within the aqueous environment of the body. Here, we adapt PEG-based hydrogels for the encapsulation and subsequent release of poorly soluble cargo, using ibuprofen as a well-characterized model compound. Building upon the A. Kloxin Lab’s approaches for the fabrication of microgels for delivery of water-soluble cargo, we investigate the release kinetics of encapsulated ibuprofen compared to a similarly sized hydrophilic compound. To evaluate the release profiles of these cargoes, we formulate hydrogels using bioorthogonal click chemistry in two geometries: bulk hydrogel discs and microgels. Bulk hydrogels provide large, local delivery depots with potential for applications such as wound dressings, while microgels offer advantages in modularity, dose control, and injectable delivery. To load hydrophobic compounds into these formats, poorly water-soluble drug cargo was first suspended in a nonaqueous solvent before being combined with PEG hydrogel precursor solutions. This mixture was then added to molds to make bulk gels or used in our established batch emulsion approach to make microgels. Following fabrication and drying, the gels were rehydrated in a physiologically relevant buffer for long-term monitoring of drug release. Developing strategies to encapsulate and release poorly water-soluble drugs within PEG-based hydrogels could broaden the utility of these materials as versatile drug delivery platforms and enable novel delivery approaches for therapeutic compounds whose limited water solubility currently restricts their applications.