Self-immolative Drug Delivery Systems based on Polycarbonate and Polyurethane Copolymers

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For an effective pharmacotherapy an optimal accumulation of a drug within an affected part of the body is required. Due to their physio chemical properties free drugs are often distinguished by a body / tissue distribution limiting the therapy success or causing unwanted side effects. Embedment into colloidal drug delivery vehicles like liposomes or nanoparticles can solve these problems, change the distribution within the organism and finally optimize the pharmacotherapy. A proper drug delivery system should address further issues to be used therapeutically. Other factors are good biocompatibility and a biodegradation yielding harmless degradation products. Further, a controlled release of the drug at the target site is required. This can be realized by “intelligent” systems utilizing different triggers like light, pH value or redox properties to release the drug in a controlled fashion.Within this project colloidal drug delivery systems based on novel switchable polymers will be investigated allowing an effective drug transport into cells and tissues. Hence, on one side the intracellular pH shift in endolysosomal compartments will be used to effectively degrade the polymer and release the drug. Further, the increased concentration of reductive glutathione (GSH), which especially can be found in tumor cells, will be used for the degradation of redox-sensitive polymers. The final goal of the project is the development of drug delivery systems being able to respond to different stimuli. Therefore, also light switchable units will be introduced that allows to release the embedded drug from the drug carrier after a short period of irradiation.