Author

Ryan C. Amos

Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Engineering Science

Program

Biomedical Engineering

Supervisor

Dr. Elizabeth R. Gillies

Abstract

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'oxide) (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.

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