Polymers with stimulation responsive degradation

In this project we propose to develop water soluble polymers with a trigger-stimulated response that maintain a stable and well-defined structure, before degrading rapidly to small molecules in response to a given stimulus. For this purpose we will use polyphosphazenes, which are unique in the fact they possess a highly hydrolytically instable backbone, which can be stabilized through the addition of certain organic side groups that protect the backbone from hydrolytic attack. Through careful design of the polymers, it is proposed that it should be possible to prepare stable polymers that hydrolyse rapidly to small molecules when the protecting organic side groups are removed. Through combining this approachwith the living cationic polymerization procedure, high molecular weight, amphiphilic/water-soluble, responsive polymers with well-defined sizes and structures will be prepared. In order to achieve the goal of truly responsive polymers, various potential stimuli will be investigated: Firstly, polymers which can be excited by an external photochemical stimulus will be prepared, with a particular focus on the preparation of materials that degrade in response to light in the near-infrared region. Secondly, enzymatic and reducible systems, triggered by cell-internal stimuli will be prepared. Such polymers would have significant promise in biomedical applications, for example in controlled drug release, and in this respect the in-vitro biodegradation and biocompatibility of the prepared polymers will also be assessed in the final stages of this project.

In this project we developed a range of polymer based materials incorporating a degradation switch, that is, materials that maintain a stable and well-defined structure until exposed to a certain stimulus upon which they become instable and thus degrade rapidly to small molecules. Three stimuli were selected and polymers prepared to respond to these. Firstly, polymers that would degrade only in response to the presence of certain enzymes. This was achieved by attaching certain peptide sequences to the polymers which are detected and cleaved by respective enzymes. These materials have particular promise in drug delivery since they can be made to degrade in the presence of enzymes present in certain cells of the body, hence potentially release any drug loaded in them. The second stimulus investigated was oxidation. Stressed and diseased tissue often have a high concentration of reactive oxygen species, hence we designed polymers which would degrade in the presence of such species. We investigated these materials for the imaging of diseased tissue and developed a system which selectively released gold nanoparticles from their formulation when exposed to higher levels of oxidative species. Since gold particles produce a contrast for imaging, this method could be used for imaging diseased areas of the body. Finally we developed light responsive polymer. While most polymer materials will degrade when exposed to high energy UV irradiation, the key here was to develop materials which disintegrate under irradiation in the visible and near infrared region, so that they can be used safely in biological tissue without causing damage to the surroundings. A variety of chemistries were developed to achieve this and we were able to prepare materials to cleave specifically under certain mild lasers. These proof-of-principle polymer-based materials can effectively be removed with low energy, gentle light sources. Future work will look to optimize the degradation rates and apply these to real life applications.