Self-immolative polydisulfides and their use as nanoparticles for drug delivery systems

Over the last few decades, nanotechnology has established to be a promising field in medicine. A remaining dominant challenge in today's pharmacotherapy is the limited selectivity of active pharmaceutical ingredients and associated undesirable side effects. Controlled drug release can be promoted by smart drug delivery systems, which release embedded API primarily depending on specific stimuli. Consequently, also the microenvironment of tumor tissue can be used advantageously. Dithiothreitol (DTT) based self-immolative polydisulfides were synthesized that preferentially respond to pathologically increased glutathione (GSH) concentrations, as found in solid tumors. The synthesis with different degrees of polymerisation was investigated as well as the synthesis of a copolymer consisting of dithiothreitol and butanedithiol (BDT). Toxicity tests were carried out on pure polymers and their degradation products. The ability to degrade was examined at pathological and physiological glutathione concentrations in order to test the suitability of the polymer as a matrix for nanoparticulate carrier systems. In addition, the processability of one polymer into nanoparticles was investigated as well as the degradation behaviour with glutathione.