(591f) Mitigating the Bioactivity Loss of Polymer- Insulin Conjugate
AIChE Annual Meeting
2017
2017 Annual Meeting
Materials Engineering and Sciences Division
Biomaterials for Drug Delivery II: Micellar, Polymer and Protein Based Drug Carriers
Wednesday, November 1, 2017 - 4:45pm to 5:03pm
There is significant interest in pursuing polymerâprotein conjugation to obtain a better protein drug with improved pharmacokinetics. However, a generic problem with polymerâprotein conjugation is that the polymers drastically reduce the bioactivity of the modified protein. Take the widely known PEGylation strategy for example, conjugating polyethylene glycol (PEG) to protein through conventional covalent coupling chemistry resulting in polymer chains non-selectively attached on the protein surface groups (e.g., amines), and potential attachment near to the proteinâs active site significantly inhibit the protein from performing designated biological function (e.g., amine group on Gly A1 of insulin). Alternatively, PEG can be used to modify the protein through site-specific conjugation technique, such as involving re-engineering the proteins. But the resulting conjugation product is still subject to bioactivity loss. In general, it appears that no matter which site of the protein the polymer is conjugated to, most resulting polymer-protein conjugates inevitably suffer from bioactivity loss. Here we present a potential strategy using zwitterionic polymers for protein conjugation to mitigate the bioactivity loss, and the development of zwitterionic polymer-insulin conjugate as a novel pharmaceutical agent.