Reactive Oxygen Species-Responsive Polymer Nanoparticles to Improve the Treatment of Inflammatory Skin Diseases

[Image: see text] To improve the quality of life for people living with chronic inflammatory skin diseases, we propose a new treatment strategy by exploring a stimuli-responsive drug delivery system. Formulations designed by exploiting smart materials can be programmed to perform a specific action upon exposure to disease-related stimuli. For instance, increased levels of reactive oxygen species (ROS), especially the accumulation of hydrogen peroxide, can be utilized to differentiate between healthy and inflamed tissues. In this concept-proofing study, the polymer poly(1,4 phenyleneacetone dimethylene thioketal) (PPADT) was investigated for its ROS-responsive properties and potential to treat inflammatory skin diseases. PPADT nanoparticles were formulated by oil-in-water emulsification followed by solvent evaporation and characterized by size, zeta-potential, and release kinetic profiles. Release profiles revealed that the PPADT nanoparticles were sensitive toward elevated levels of ROS in an ROS-stimulus concentration (0.1–10 mM) and time-dependent manner (flare-up mimicked). The safety assessment proved that the PPADT polymer and the monomers generated by oxidation do not show any sign of being cytotoxic to fibroblasts and no mutagenic liabilities were observed. In conclusion, the PPADT polymer demonstrated to be a promising material for stimuli-responsive delivery of hydrophobic small molecules in the treatment of inflammatory skin diseases.