Mechanically Tuneable Physical Nanocomposite Hydrogels from Polyelectrolyte Complex Templated Silica Nanoparticles for Anionic Therapeutic Delivery

Hydrogels have shown great promise for drug delivery and tissue engineering but can be limited in practical applications by poor mechanical performance. The incorporation of polymer grafted silica nanoparticles as chemical or physical crosslinkers in in situ polymerised nanocomposite hydrogels has been widely researched to enhance their mechanical properties. Despite the enhanced mechanical stiffness, tensile strength, and self-healing properties, there remains a need for the development of simpler and modular approaches to obtain nanocomposite hydrogels. Herein, we report a facile protocol for the polyelectrolyte complex (PEC) templated synthesis of organic-inorganic hybrid poly(ethylenimine) functionalised silica nanoparticles (PEI-SiNPs) and their use as multifunctional electrostatic crosslinkers with hyaluronic acid (HA) to form nanocomposite hydrogels. Upon mixing, electrostatic interactions between cationic PEI-SiNPs and anionic HA resulted in the formation of a coacervate nanocomposite hydrogel with enhanced mechanical stiffness that can be tuned by varying the ratios of PEI-SiNPs and HA present. The reversible electrostatic interactions within the hydrogel networks also enabled self-healing and thixotropic properties. The excess positive charge present within the PEI-SiNPs facilitated high loading and retarded the release of the anionic anti-cancer drug methotrexate from the nanocomposite hydrogel. Furthermore, the electrostatic complexation of PEI-SiNP and HA was found to mitigate haemotoxicity concerns associated with the use of high molecular weight PEI. The method presented herein offers a simpler and more versatile strategy for the fabrication of coacervate nanocomposite hydrogels with tuneable mechanical stiffness and self-healing properties for drug delivery applications.