Harnessing Hydrogel Interaction with Functional Polymeric Nanoparticles for Sustained Co-Delivery of Therapeutics

High Resolution Image Download MS PowerPoint Slide The combination of hydrogels and polymeric nanoparticles (NPs) offers a versatile strategy to engineer multifunctional nanocomposite systems for advanced drug delivery applications. In this work, three amphiphilic block copolymers were synthesized through controlled/living polymerizations, affording macromolecules with distinct end-chain functionalities. These copolymers self-assembled into core-shell NPs, which were subsequently embedded within a cross-linked agarose-carbomer-hyaluronic acid hydrogel via physical, chemical, or ionic interactions. The incorporation of NPs within the hydrogel matrix enabled the co-delivery of both hydrophobic and hydrophilic therapeutic cargos, confining dexamethasone (DEX) in the hydrophobic NP core and a model protein within the water-rich hydrogel network. The resulting hybrid systems exhibited tunable rheological and NP release properties, depending on the NP surface moieties and the encapsulation method. Sustained DEX release was displayed over several days, and controllable protein release was achieved according to the NP surface properties. The nanocomposite showed excellent cytocompatibility, demonstrating a relevant reduction of pro-inflammatory cytokines expression in vitro . Overall, the proposed strategy highlights the potential of polymer chemistry-driven design to tailor hydrogel-NP interactions, providing a promising platform for targeted, sustained co-delivery of therapeutics suitable for several applications.