Heather D. Maynard*

 

Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA 90095, USA

 

Therapeutic proteins are challenging to transport and store, and thus the majority need to be refrigerated or frozen.  Proteins exposed to changes in temperatures and mechanical agitation often lose activity.  This can be harmful or even fatal for patients that take the medications and can also increase costs because of the requirement of a cold chain.  Thus, polymeric materials that are capable of stabilizing biomolecules at room temperature and to agitation are of significant interest.1  This talk will focus on new polymers and nanogels to address this important problem. Well defined polymers prepared by controlled radical polymerization and ring opening polymerization were tested in their ability to stabilize proteins to room temperature, elevated temperatures, mechanical agitation, and pH changes when added as excipients.2,3,5  Side chains derived from Nature and others from known excipient classes were compared and contrasted, and the mechanisms of stabilization were investigated. Grafting to and grafting from strategies were utilized to prepare protein conjugates of these polymers, and in vivo testing showed that the polymers significantly increased blood circulation times (i.e. pharmacokinetics) in addition to retaining protein activity after exposure to high temperatures.4  Nanogels that stabilize sensitive proteins and degrade upon a bio-stimulus were also prepared and evaluated.  Synthesis and stabilization properties and application of the polymers and nanogels to proteins used to treat diabetes and cancer will be presented in this talk.

 

References

  1. Pelegri-O’Day, E. M.; Maynard, H. D. “Controlled Radical Polymerization as an Enabling Approach for the Next Generation of Protein-Polymer Conjugates,” Acc. Chem. Res., 2016, 49, 1777-1785.
  2. Mancini, R. J.; Lee, J.; Maynard, H. D., “Trehalose Glycopolymers for Stabilization of Protein Conjugates to Environmental Stressors,” J. Am. Chem. Soc., 2012, 134, 8474-8479.
  3. Lee, J.; Lin, E.-W.; Lau, U. Y.; Hedrick, J. L.; Bat, E.; Maynard, H. D., “Trehalose Glycopolymers as Excipients for Protein Stabilization,” Biomacromolecules, 2013, 14, 2561-2569.
  4. Liu, Y.; Lee, J.; Mansfield, K. M.; Ho, J. K.; Sallam, S.; Wesdemiotis, C.; Maynard, H. D. “Trehalose Glycopolymer Enhances Both Solution Stability and Pharmacokinetics of a Therapeutic Protein,” Bioconjugate Chemistry, 2017, 28, 836-845.#
  5. Pelegri-O’Day, E. M.; Paluck, S. J.; Maynard, H. D. “Substituted Polyesters by Thiol-ene Modification: Rapid Diversification for Therapeutic Protein Stabilization,” J. Am Chem. Soc., 2017, 139, 1145-1154.