Unlocking the Potential of Poloxamine 908 for Injectable Nanocomposite Hydrogels: Rheological Performance,...

Background/Objectives: Poloxamine 908 (P908), an amphiphilic block copolymer with thermo- and pH-responsive properties, was demonstrated to be a biomaterial that can be employed for the development of injectable hydrogels. The present study aimed to investigate the influence of nanoparticles with different chemical compositions and surface properties on the properties of P908 hydrogels. Methods: Poloxamer 188 (P188)-PLGA, P188-zein and sodium deoxycholate (SD)-zein nanoparticles obtained by nanoprecipitation were incorporated into 30% (w/w) P908 hydrogels using the cold preparation method. The formulations were characterized by rheological analysis, dissolution studies, FT-IR spectroscopy, in vitro release analysis using rutin as a model compound, and DPPH radical scavenging assay to evaluate the bioactivity of nanoparticles contained within the hydrogel matrix. Results: The incorporation of nanosystems preserved the injectability and thermoresponsive behavior of P908 hydrogels and affected their rheological and dissolution properties in different ways. P188-PLGA NPs increased viscosity by approximately 23%, whereas P188-zein NPs caused a slight decrease of approximately 9%, compared with plain P908 at 37 °C and 1 s^-1. Both formulations showed a moderate increase in T_sol-gel, reaching 28.5 and 28.8 °C, respectively, compared with 26.4 °C for plain P908 systems. A more pronounced effect was observed with SD-zein NPs, which reduced viscosity by approximately 29% and shifted T_sol-gel to 33.9 °C. Moreover, SD-zein NPs enhanced hydrogel dissolution under acidic conditions, with complete dissolution occurring after 6 h at pH 5.0 compared with 8 h at pH 7.0. FT-IR demonstrated the effective inclusion of the colloidal systems within the P908 matrix. Nanocomposite hydrogels provided a more sustained release of rutin with respect to that obtained without the copolymeric matrix, with positively charged P188-zein nanosystems showing an enhanced release at acidic pH, likely due to electrostatic repulsion with the protonated P908 network. DPPH assay confirmed that the inclusion of rutin-loaded nanoparticles into P908 hydrogels preserved the antioxidant activity of the active compound, with a slight increase in radical scavenging capacity, due to the intrinsic mild antioxidant capacity of the copolymeric matrix. Conclusions: P908 is a suitable biomaterial to develop nanocomposite hydrogels. The composition and surface properties of nanoparticles allow for the modulation of hydrogel features, enabling the design of therapeutic formulations with tailored rheological properties and characteristics of drug release.