Date of Award

Fall 12-2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Polymers and High Performance Materials

Committee Chair

Daniel A. Savin

Committee Chair Department

Polymers and High Performance Materials

Committee Member 2

Robert Y. Lochhead

Committee Member 2 Department

Polymers and High Performance Materials

Committee Member 3

Sarah E. Morgan

Committee Member 3 Department

Polymers and High Performance Materials

Committee Member 4

Derek L. Patton

Committee Member 4 Department

Polymers and High Performance Materials

Committee Member 5

Robson F. Storey

Committee Member 5 Department

Polymers and High Performance Materials

Abstract

The goal of this dissertation was to tune the pH response and self-assembled morphologies of amphiphilic polypeptide block copolymers for use as drug delivery vehicles. Poly(L-lysine) and poly(L-glutamtic acid) are responsive, ionizable polypeptides that undergo secondary structure transitions, from α-helix to random coil, whereby the change in conformation of the peptide chain results in changes to the global morphology of a self-assembled system. The main focus of this work was to understand how changes in the polymer composition and the local environment can lead to control over the behavior of the overall system. First, the responsive behavior of poly(L-lysine) block copolymers was studied in the presence of ionic liquids to determine how the assembly and response of the peptide was affected by the presence of an organic salt. Next, changes in the ring-opening polymerization of amino acid N-carboxyanhydride monomers were made to alter to the composition of homo-block polypeptides to statistical copolypeptides. An α-helix forming amino acid, leucine, was incorporated into the peptide chain to space charged lysine units from one another in order to alter the pH at which its secondary structure transition occurs. Leucine blocks were incorporated into linear block copolymers to afford more stability to the assembly as well as the capability of achieving novel morphologies. Finally, some of these materials have shown efficacy in controlled release of a loaded drug over an extended period of time at different pH and salt concentrations.

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