04/24/18 - 9:45 AM to 11:00 AM
Student Seminar Series: Professor Heather D. Maynard
Student Seminar Series
"Fluorous, Trehalose and PEG Containing Degradable Polymers and Nanoparticles for Medical and Agricultural Applications"
Functional synthetic polymers and nanoparticles are important in a variety of fields. For many applications, controlled degradation is desirable or even necessary to fulfil design requirements. This talk will focus on three classes of degradable polymers and nanoparticles that we have developed for different applications. The first class is based on polymers where the backbone degradability is controlled by fluorous side chain content. Specifically, we synthesized copolymers containing poly(ethylene glycol methyl ether methacrylate) (PEGMA), fluorous methacrylate (1H,1H,2H,2H-perfluorooctyl or 1H,1H,2H,2H,3H,3H-perfluoropentyl methacrylate), and the cyclic ketene acetal 5,6-benzo-2-methylene-1,3-dioxepane (BMDO) by controlled radical polymerization. The polymers assembled into single-chain nanoparticles or multi-chain nanoparticles depending on the fluorous content. The fluorous content also controlled the degradation rate of the nanoparticles; specifically, the degradation rate constant for the highest fluorous content polymer was one hundred-fold smaller compared to the non-fluorous polymer. This was shown by spectroscopic data to be due to the local environment rather than the self assembled structures themselves. Thus, fluorous content is an excellent way to control degradation of nanoparticles based on poly(PEGMA). The second class of polymers and nanoparticles is based on trehalose glycopolymers. Specifically, polyesters with side chain trehalose and trehalose glycopolymers containing pendant pyridyl disulfide groups were synthesized. The former stabilize an important therapeutic granulocyte colony-stimulating factor (GCSF) and degrade by hydrolysis. The latter polymers were subsequently cross-linked into nanoparticles utilizing the important hypoglycemia therapeutic peptide glucagon, which was modified to contain two free thiols. As a result, the peptide loading content was high, the peptide was bioactive in vitro, and it was readily released in reducing environments. Most importantly, the trehalose glycopolymer nanoparticle protected the glucagon from aggregation for at least three weeks and also to neutral pH, while the native peptide aggregates within hours under these conditions. The third class of nanoparticles is based on poly(ethylene glycol) (PEG) and cross-linking is accomplished utilizing oxime and hydrazone chemistries. Depending on the imine chemistry utilized, the degradation of hydrogels and nanoparticle can be controlled. These materials are being utilized to incorporate chemicals for agricultural applications for controlled delivery. This talk will cover in detail the synthesis of the various polymers, the formation of nanoparticles, characterization and degradation. In addition, applications specifically in medicine and agriculture will be disclosed.
Heather D. Maynard received a Bachelor of Science with Honors in chemistry from the University of North Carolina at Chapel Hill, and a doctorate in chemistry from the California Institute of Technology in 2000 for research with Nobel Prize winner Robert H. Grubbs. She then moved to the Swiss Federal Institute of Technology in Zurich (ETH), where she was an American Cancer Society Post-doctoral Fellow with Jeffrey Hubbell from 2000-02. Maynard joined the University of California, Los Angeles (UCLA), faculty as an assistant professor in August 2002 as the first Howard Reiss Career Development Chair in the Department of Chemistry and Biochemistry, and as a member of the California NanoSystems Institute. She is now a full professor and Myung Ki Hong Endowed Chair in Polymer Science, director of the Chemistry Biology Interface Training Program, and associate director of Technology and Development for the California NanoSystems Institute. Maynard has received the Amgen New Faculty Award, National Science Foundation Career Award, Seaborg Award for Outstanding Research, the Hanson-Dow Award for Excellence in Teaching, an Alfred P. Sloan Fellowship, the Herbert Newby Award for Outstanding Research and the Arthur Cope Scholar Award for 2018. Maynard is an American Chemical Society POLY, American Chemical Society PMSE, Leverhulme, Kavli Frontiers, and Royal Society of Chemistry Fellow, and was recently awarded a Fulbright Specialist Grant for New Zealand. She was also selected to be a member of the US Defence Science Study Group from 2016-2017. Maynard is on the editorial boards of Polymer Chemistry and Chem and the editorial advisory boards of the Journal of the American Chemical Society, Biomacromolecules, Bioconjugate Chemistry, Journal of Polymer Science A: Polymer Chemistry, and Macromolecular Biosciences. Maynard’s research interests focus on the design and synthesis of biomimetic and biohybrid polymers and hydrogels for applications in protein drug stabilization and delivery.