Fine-Tuning Biodegradable Polymersome Membrane Permeability by the use of a Fine-tuned Polypeptoid Composition
Biomaterials
Final Report Abstract
In Summary, 3 main goals have been achieved. First of all, peptoids were synthesised and formed vesicles. Secondly, polyesters for biodegradable polymersomes were successfully synthesised. And last, but not least, a miktoarm star terpolymer could be synthesised, allowing the production of stable patchy polymersomes . The peptoids were synthesised using an automated solid-phase synthesis in a sub-monomer approach, which is widely described in the literature by Zuckermann et al. I synthesised 4 different peptoids where all of them had the same hydrophobic part (pentyl side chain), but different hydrophilic parts. Peptoids with a methoxyethyl side chain in the hydrophilic part proved to be of lowest dispersity and formed vesicles more readily than other peptoids investigated (OEG side chain and hydroxyethyl side chain). Despite of notable differences, all peptoids investigated did from vesicles. Together with Dr Ilaria Romano and Dr Loris Rizello we investigated polyesters for biodegradable polymersomes. Our polyesters were based on fumarate for eventual anti-inflammatory effects. The polyester of the hydrophobic part was achieved by polycondensation and then combined with PEG or PMPC and hydrophilic parts. Vesicles could be formed of both polymers and they could also be degraded using esterase enzymes. Starting toxicity data indicated that these polyesters can be prepared in a biocompatible way. A miktoarm star polymer was synthesised to ensure stable patchy polymersomes. The star could be achieved using three click-like reactions onto a central dibromomaleimide core. The bromine atoms could be displaced using thiol units from previously functionalised polymers. A classic CuAAC reaction yielded the final star. Once the star terpolymer was available, it was combinded with a linear amphiphilic block-copolymer. When used in combination, they resulted in vesicles where the size of the different domains (patches) could be regulated by the amount of star polymer added.
Publications
- Curr. Opin. Pharmacol. 2014, 18, 104
Messager, L.; Gaitzsch, J.; Chierico, L.; Battaglia, G.
(See online at https://doi.org/10.1016/j.coph.2014.09.017) - Polym. Chem. 2015, 6, 2065
Ruiz-Perez, L.; Madsen, J.; Themistou, E.; Gaitzsch, J.; Messager, L.; Armes, S. P.; Battaglia, G.
(See online at https://doi.org/10.1039/c4py01508h) - Chemical Reviews 2016
Gaitzsch, J.; Huang, X.; Voit, B.
(See online at https://doi.org/10.1021/acs.chemrev.5b00241)
