From Macromolecular Design to Supramolecular Self-assembly

Abstract: Advancements in drug delivery have enabled a wider array of prevention, control and treatment of diseases such as cancer. Drug delivery systems have the possibility of encapsulating drugs with low solubility, delivering them to specific locations in the body as well as obtaining a controlled and sustained drug release. The systems used today range over a wide structural and compositional area, where liposomes as well as nanotubes have been used as vehicles. Polymeric micelles also play an important role as drug carriers and have gathered great attention due to their versatility.The optimization of these micelle systems is critical in order to enhance their effect. In this work three strategies were designed for the tailoring of micelle behavior in order to induce desirable and controllable micelle properties.The influence of polymer architecture upon self-assembly was facilitated by designing a novel synthetic pathway yielding cyclic polypeptides. The initiation route using amidine or guanidine bases induced zwitterionic polymerization and hence resulted in cyclic polypeptides. A strategy using the crystallinity of the micelle core to tailor micelle behavior was accomplished. By solely using the core crystallinity, tuning of the critical micelle concentration, micelle size as well as loading and release of hydrophobic molecules was achieved. The induction of redox-responsiveness and electroactivity, through the introduction of aniline pentamer into amphiphilic PEG-PLA, gave rise to time-dependent dissociation (triggered release) of the micelles without external stimuli.A powerful toolbox has been created for the tailoring of micelle behavior. By combining these tools, the design of optimized drug carriers for specific applications is enabled.