RUI: Self-Assembled PEG-Peptide Copolymers for Biomedical Applications

Williams College, Williamstown MA

Investigators

Abstract

ID: MPS/DMR/BMAT(7623) 0804444 PI: Goh, Sarah ORG: Williams College Title: RUI: Self-Assembled PEG-Peptide Copolymers for Biomedical Applications INTELLECTUAL MERIT: The broad goal of this proposal is to develop polymeric micelles for biomedical applications from amphiphilic poly(ethylene glycol)- block-peptide copolymers with peptide segments (conjugates) that display lower critical solution temperatures (LCSTs). Amphiphilic block copolymers self-assemble to form stable micelles with hydrophobic cores to encapsulate hydrophobic drugs. With an LCST range of 22-35°C, these biomimetic polymers will undergo an additional assembly of the hydrophobic peptides, further stabilizing the micellar delivery vehicle. The relationships between copolymer structure, LCST, micellization behavior, and peptide secondary structure for this class of amphiphiles are not well understood. A fundamental study of these relationships is proposed by varying the length of each polymer block, the peptide identity, and the copolymer architecture. Peptides with known LCST behavior will be investigated, in particular, the elastin-like peptide (ELP) VPGVG, as well as hydrophobic peptides that demonstrate secondary structures, such as poly(valine), poly(proline), and poly(alanine). Both linear and branched copolymer architectures will be synthesized using a combination of standard peptide coupling techniques and reversible addition fragmentation chain transfer (RAFT) controlled polymerization methods. The proposed research has the following objectives: (1) Identify key structural requirements for micelle formation in PEG-ELP copolymers. (2) Discover new peptide sequences that form LCST-based biomaterials. (3) Evaluate the efficacy of PEG-peptide copolymers as drug delivery vehicles. By carrying out these experiments, the project will elucidate the effects of structure and polymer properties as they relate to performance of micellar drug delivery vehicles. BROADER IMPACTS: Tunable vehicles for delivery of drugs, genetic material, and contrast agents have not yet been perfected. This proposal offers a new approach that is well worth pursuing. The proposal provides a model for integration of research and education at the undergraduate level. The project lends itself to being subdivided into modules differing in scope and complexity so that undergraduate students at all levels can participate effectively. Each undergraduate will be given an individual project, but they will work together to advance the overall aims of the proposal. Each student will be responsible for a primary literature search for relevant information concerning their own project. The PI provides clear and explicit detail about her laboratory management procedures and describes the group meeting experiences that will be provided to integrate the several components and to ensure that each student knows not only about his/her own component but understands how it fits with the overall goals. Reports, theses, manuscript drafting, and group meetings, along with opportunities to present at regional and national meetings, will allow the students to develop their skills at communicating the intellectual context and research results of the overall project.