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The synthesis and optimization of functionalized hyperbranched polyglycerols as potential topical hemostatic agents

University of British Columbia

As a classical representative of the hyperbranched polymer family, hyperbranched polyglycerol has been applied in a variety of diagnostics and therapies. After functionalizing the end groups with zwitterionic sulfabetaines (SB) and cationic quaternary amines (QA), the polymer exhibited superior hemagglutination capacity at a concentration ≥ 1 mg/mL and erythrocyte lysis was not observed. The goal in the present work is to use the monomers above to maximize the polymer adhesion to cells while eliminating the membrane damage caused by multivalent polycation exposure. The desired stickiest structure is a novel attractive bioadhesive material which may serve as a future topical hemostatic agent for bleeding wounds, overcoming the limitations of existing products in the market. To this end an optimization was performed on the synthesis scheme to achieve a library of HPG based polymer conjugates with a constant amount of one derivative (SB/QA) and a varied number of the other derivative (QA/SB). The efficacy of sulfabetaine (SB) and quaternary amine (QA) was quantified and different hemagglutination behaviors were displayed. Hemolysis, cytotoxicity and inhibition effects as well as the hydration properties of the polymer conjugates were also evaluated. In the blood aggregation analysis, HPG-SB₃₀-QA₃₀-OH₄₀ and HPG-SB₃₀-QA₄₀-OH₃₀ exhibited strong red blood cells aggregation effects even at a concentration as low as 1mg/mL. Thirty percent of SB also reduced the hemolytic activity to an undetectable level and retained high cell viability in the presence of 30% QA. The bound water of each repeat monomer unit was quantified by differential scanning calorimetry and explained the fouling resistance behavior of the cells. The addition of linear polyglycerol sulfate into the HPG-SB-QA-OH system effectively suppressed the red blood cell aggregation, which indicated the possibility of reversibly applying the materials for hemostasis. Overall, the in vitro studies suggest that the stickiest structure of the designed functionalized HPG is HPG-SB₃₀-QA₃₀-OH₄₀, which is biocompatible and harmless to cells.

Text

2018-03-12

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/64782

Chemistry

University of British Columbia

UBCV

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