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

对于有效的药物治疗，需要药物在身体受影响部位内的最佳积累。由于其生理化学性质，游离药物通常通过限制治疗成功或引起不希望的副作用的身体/组织分布来区分。将药物包埋到胶体药物载体如脂质体或纳米颗粒中可以解决这些问题，改变药物在机体内的分布，最终优化药物治疗。适当的药物递送系统应该解决治疗上使用的进一步问题。其他因素是良好的生物相容性和生物降解产生无害的降解产物。此外，需要药物在靶位点的受控释放。这可以通过“智能”系统来实现，该系统利用不同的触发器，如光、pH值或氧化还原特性，以受控的方式释放药物。在该项目中，将研究基于新型可转换聚合物的胶体药物递送系统，从而有效地将药物转运到细胞和组织中。因此，一方面，内溶酶体隔室中的细胞内pH变化将用于有效降解聚合物并释放药物。此外，增加浓度的还原性谷胱甘肽（GSH）（其尤其可在肿瘤细胞中发现）将用于氧化还原敏感性聚合物的降解。该项目的最终目标是开发能够对不同刺激做出反应的药物输送系统。因此，还将引入光可切换单元，其允许在短时间照射后从药物载体释放嵌入的药物。

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.