Hybrid Titanium Oxide/Polymer Amphiphilic Nanomaterials with Controlled Size for Drug Encapsulation and Delivery

This work describes for the first time the synthesis of hybrid drug-loaded TiO₂/polymer amphiphilic nanoparticles of finely controlled size utilizing a simple and reproducible sol–gel process that comprises the formation of a titanium(IV)/acetone oxo-organo complex followed by its blending with an amphiphilic poly(ethylene oxide)-b-poly(propylene oxide) block copolymer in acetone and its aqueous-phase nanoprecipitation. The size of the hybrid nanoparticles is governed by the complex aging, e.g., hybrid nanoparticles display diameter between 228 and 53 nm for aging of 1 and 36 days, respectively (dynamic light scattering). In addition, they show excellent physical stability in water owing to the coating of the surface with poly(ethylene oxide) blocks of the copolymer. Conversely, polymer-free TiO₂ particles are large and precipitate fast. Incorporation of a model hydrophobic drug, nitazoxanide, to the precursor solution results in hybrid nanoparticles containing 12.9% w/w cargo that is released following a bimodal profile. High-resolution transmission electron microscopy (Titan Cubed Themis G2 300) analysis reveals the porous amorphous nanostructure of these novel hybrids and colocalization of drug and copolymer in the nanoparticle bulk. Finally, upon ultrasonication, our hybrid nanoparticles produce reactive oxygen species in vitro which paves the way for their use in sonodynamic and drug release therapies.