Surface Functionalization of Polymer Vesicles with Dendritic Groups: Effects on Physical and Biological Properties

Polymer vesicles (polymersomes) are spherical assemblies with aqueous cores, formed by the self-assembly of amphiphilic polymers in an aqueous environment. They resemble phospholipid vesicles, but typically exhibit much greater stabilities. The chemical versatility of the polymer synthesis makes it possible to tune the vesicle characteristics such as vesicle size and: circulation time in vivo. As such, they are highly promising materials for various applications including drug delivery. Our research group recently developed a versatile approach for the conjugation of dendritic groups to the surfaces of polymer vesicles which allows the surface properties to be readily tuned for specific biological properties or applications. This thesis will investigate the effects of different dendron functionalities, both neutral and cationic, on the rate of release of encapsulated small molecules and larger biomacromolecules, cytotoxicity and the cell uptake properties of polymer vesicles. These properties were explored in both non-biodegradable vesicles based on polybutadiene-poly(ethylene oxide) (PBD-PEO) and biodegradable vesicles based on polycaprolactone-poly(ethylene\u27oxide) (PEOPCL). The rate of release of an encapsulated small molecule, rhodamine B, was founk to be dependent on the absence or presence of dendritic functionality. Unlike with small molecules, the release of encapsulated protein, bovine serum albumin (BSA), depends on the charge of the dendritic functionalization since both cationic systems exhibited faster, similar release profiles. The cytotoxicity of the vesicle systems was found to be dependent on their surface charge as toxicity was observed with both cationic systems at higher concentrations. Finally, the cell uptake was found to be dependent on the functional group displayed on the vesicle surface and guanidine functionalized vesicles had significantly increased cell uptake relative to the other samples