Design of Injectable Nanocomposite Hydrogels for Controlled Release of Nanoparticles

Nanocomposite hydrogels, i.e.; a combination of hydrogels and nanoparticles, have emerged as a promising platform for drug delivery owing to the high degree of design flexibility. Despite the wealth of literature on nanocomposite hydrogels, there is scant experimental data on the release of drug-loaded nanoparticles from hydrogels. Here, we report on the incorporation and subsequent release of dye-loaded nanoparticles from alginate-based hydrogels. We investigated the rheological properties of alginate and alginate-poly(ethylene oxide) hydrogels as a function of nanoparticle loading, as well as the time-dependent nanoparticle release profiles. The effects of hydrogel compositional parameters and nanoparticle loading on viscosity and release profiles were investigated using principal component analysis (PCA) and partial least-squares regression (PLSR), respectively. Additionally, the release profiles were fit using Zero and First-order models as well as the Higuchi, Hixson-Crowell and Korsmeyer-Peppas kinetic models for drug release. We found that the effect of nanoparticle concentration on gel viscosity is strongly dependent on the alginate concentration, with nanoparticles contributing to the gel structure at higher polymer concentrations. Release of nanoparticles from the hydrogels was well fit by a modified first-order kinetic model, comprising a significant burst followed by a concentration-dependent release of nanoparticles. Collectively, our findings provide insight into how hydrogels can be used as reservoirs for controlled delivery of nanoparticles.