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Document Type

Open Access

Degree Program

Molecular & Cellular Biology

Degree Type

Master of Science (M.S.)

Year Degree Awarded

2011

Month Degree Awarded

September

Keywords

polymer, in vivo, breast cancer

Abstract

Polymer conjugates offer a way to introduce materials into the body that would normally be rejected or cause toxicity. Two polymers are investigated in vivo for uses in chemotherapeutic delivery, protein therapeutics, and DNA transfection. A novel polymer, polyMPC, has the ability to increase doxorubicin loading and its solubility, and is conjugated in a way to release its payload in a low pH environment. Through its conjugation, blood clearance time of doxorubicin is increased, and thus tumor exposure to the drug is increased with a single administration. It can be administered at ten times the concentration of free doxorubicin, and three times the concentration of Doxil®, while decreasing the cardio-toxicity normally associated with doxorubicin administration. These results show that polyMPC has the potential to increase treatment efficacy of doxorubicin. With increased circulation time, MPC polymers have additional potential for protein delivery and variations of its design were tested in linear, branched and grafted states, which show limited affect on tissue weight. An additional polymer for use in DNA transfection, NLS2, demonstrated its lack of tissue toxicity when injected intramuscularly. While continued investigation into these polymers is required, this initial data indicates their promising uses as therapeutics.

First Advisor

Sallie Smith Schneider

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