Polyester dendrimers for biomedical applications
Time: Fri 2020-05-15 09.00
Subject area: Fibre and Polymer Science
Doctoral student: Patrik Stenström , Ytbehandlingsteknik
Opponent: Professor Javier de la Mata, University of Alcalá, Spanien
Supervisor: Professor Michael Malkoch, Ytbehandlingsteknik, Fiber- och polymerteknologi, Polymerteknologi
Dendrimers are perfectly defined and highly branched large molecules with a high density of functional groups that makes them interesting for a variety of biomedical applications such as drug delivery, theranostics and as antimicrobials. Their synthesis can be complicated, time-consuming and expensive which has been an obstacle to their success. This work was aimed towards exploring a recently developed synthesis method for the synthesis of polyester dendrimers based on 2,2-bis(methylol)propionic acid (bis-MPA) and to evaluate these for biomedical applications. This synthesis method makes use of N,N'-carbonyldiimidazole for the formation of esters, and the reaction is catalyzed by the inorganic salt cesium fluoride. In comparison to previously established methods, this technique proved itself throughout this work as an excellent tool for the synthesis of precise ester-based structures by having no competing side-reactions and producing only easy-to-remove by-products while still being highly efficient. Complex dendrimers with multifunctionality or chargeable functional groups could be synthesized with relatively low efforts and good chemical and structural purity. Some of the charged dendrimers were found to be antibacterial, most likely due to their strong interactions with bacterial membranes, while being non-toxic to cells. New antibacterial materials are highly sought after as replacements for conventional penicillin towards which bacterial resistance is constantly increasing. These dendrimers were also incorporated into a water-absorbent gel – a hydrogel – that in turn was shown to be highly efficient at reducing the viability of bacteria. Large molecules with positive charges are also used for the delivery of short interfering RNA (siRNA) into cells. siRNA has the potential to cure a wide array of diseases by silencing the genes that causes these diseases, but it requires the aid of another molecule or particle to be efficient. The dendrimers synthesized in this work were shown to be efficient at forming complexes with siRNA, but not capable of efficiently delivering it into cells. This was most likely due to either the dendrimers degrading too fast or the interactions between the pH-dependent charges and the siRNA being too weak as the complex attempts to cross the cell membrane.