Novel dendron-polymer conjugates for drug delivery

Abstract

Multi-armed macromolecules have attracted increasing attention as polymeric scaffolds for biological applications. One of the significant ways to improve the properties of these architectures is the incorporation of dendrimers which are branched macromolecules with well-defined structures. Dendrimers provide the polymeric structure with multivalency and monodispersity especially important in bioconjugation area. First study in this thesis involves synthesis of dendron-polymer conjugates based on Diels-Alder/retro Diels-Alder strategy and drug conjugation to the periphery of these blobk copolymers. Biocompatible polyethylene glycol (PEG) is used as the polymer to provde water solubility to the hydrophobic molecules. Also, due to its anti-biofouling property, it reduces the non-specific interactions of the drug with the proteins in the body. End groups of PEG are functionalized with maleimide to undergo Diels-Alder cycloaddition with the biodegradable polyester dendrons having anthracene functionality at the core. Further functionalization of the periphery of dendron-polymer copolymers with alkyne groups yields a multifunctional dendritic polymer for bioconjugation via Huisgen type "click" reaction. The second study involves the synthesis of multiarm star polymers based on core functionalized initiators via Atom Transfer Radical Polymerization (ATRP). Dendrons bearing maleimide groups in their core are furnished with initiators at end of their arms for polymerization of several acrylates and methacrylates. It is well known that maleimide group can readily react with thiols via Michael Addition reaction. Thiol containing tripeptide gluthathione is used to demonstrate the reactivity of the maleimide bearing dendritic polymers. Since the bioavailability of the conjugated biomolecule is remarkably affected by the density of the polymer chains around it, these dendritic macromolecules have great potential for protein delivery.