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Choline phosphate : an improved synthesis and applications in red cell and platelet

University of British Columbia

Biomembrane adhesive materials that are effective in aqueous media have gained attention in the past decade owing to their broad uses such as tissue sealants and localized drug delivery agents. Here we demonstrate that hyperbranched polyglycerols (HPG) surface-modified with choline phosphate (CP) in a multivalent fashion are able to bind to eukaryotic cell membranes containing phosphatidyl choline (PC), which is structurally in a reverse orientation compared to CP. This work is dependent on a new synthesis of the CP reagent which allows an efficient production of HPG-CP. In the experimental design section, the preparation and characterization of a library of HPG molecules decorated with different densities of zwitterionic CP ligands is described. A post-polymerization pathway was followed that employs azido moieties on an HPG core for the conjugation of triple bond attached functional groups through “click” reaction, providing the desired HPG-CP macromolecule. The proportions of CP moieties were controlled by adjusting the monomer concentration. It was demonstrated that polymer conjugates carrying over 10% zwitterionic CP groups induced significant hemagglutination without causing red blood cell lysis or any cytotoxic effect. As the CP density was increased on the carrier HPG, cellular adhesion and aggregation became stronger as the intercellular contact area became maximized. The polymer conjugates, including HPG (20 kDa) decorated with 30 and 80 CP groups, were also found to be capable of activating platelets to a significant level while, interestingly, platelet aggregation tests demonstrated negative results. Future studies will investigate the mechanism of this unusual result, perhaps due to HPG-CP interacting with ADP which is intimately involved in platelet aggregation in vivo. DSC results showed that each CP ligand bound more than 37 water molecules on average, compared to each hydroxyl unit on the native HPG binding ~7, primarily owing to the dual-ion structure of CP and the multiple oxygens on the group. It is believed that the hydration ability contributed by the unique zwitterionic construct contributes to a barrier to resist biofouling on the polymer surface. These properties together render HPG-CPs potentially able to participate in various bio- or pharmaceutical- related applications with outstanding biocompatibility.

Text

2019-04-23

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/69840

Chemistry

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/