460626 Zwitterionic Gel Encapsulation Promotes Protein Stability, Enhances Pharmacokinetics and Reduces Immunogenicity

Tuesday, November 15, 2016: 2:36 PM
Imperial A (Hilton San Francisco Union Square)
Peng Zhang, Fang Sun and Shaoyi Jiang, Chemical Engineering, University of Washington, Seattle, WA

As an emerging class of therapeutics, protein drugs offer the advantages of higher specificity and potency than small molecules. However development of protein therapeutics is hindered by their poor stability, inadequate pharmacokinetic (PK) profiles, and immunogenicity. Polyethylene glycol conjugation (PEGylation) is the most successful strategy to date to overcome these shortcomings, and more than ten PEGylated proteins have been brought to market. However, anti-PEG antibodies induced by treatment raise serious concerns about the future of PEGylated therapeutics. Based on extensive studies of PEGylation, we believe that two issues are responsible for its immune response: the immunogenicity/antigenicity of PEG itself, and limited PEG coverage on the protein surfaces. By solving these two issues, we demonstrate a zwitterionic polymer network encapsulation (ZPNE) technology that effectively enhances protein stability and pharmacokinetics while reducing the immune response. Highly immunogenic fungal-derived uricase was used as a model therapy. In this study, uricase modified with a comprehensive zwitterionic polycarboxybetaine (PCB) gel network exhibited exceptional stability and a greatly prolonged circulation half-life. More importantly, the PK behavior was unchanged and neither anti-uricase nor anti-PCB antibodies were detected after three weekly injections in a rat model. This technology is applicable to a variety of proteins and unlocks the possibility to adopt highly immunogenic proteins for therapeutic or protective applications.

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See more of this Session: Biomaterials: Graduate Student Award Session
See more of this Group/Topical: Materials Engineering and Sciences Division