Kinetic study of all-or-none hemolysis induced by cationic amphiphilic polymethacrylates with antimicrobial activity

doi:10.1016/j.cclet.2015.01.029

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Abstract

To gain an understanding of the toxicity of antimicrobial polymers to human cells, their hemolytic action was investigated using human red blood cells (RBCs). We examined the hemolysis induced by cationic amphiphilicmethacrylate random copolymers, which have amino ethyl sidechains as cationic units and either butyl or methyl methacrylate as hydrophobic units. The polymer with 30 mol% butyl sidechains (B₃₀) displayed higher hemolytic toxicity than the polymer with 59 mol% methyl sidechains (M₅₉). B₃₀ also induced faster release of hemoglobin from RBCs than M₅₉. A new theoretical model is proposed based on two consecutive steps to form active polymer species on the RBC membranes, which are associated to RBC lysis. This model takes the all-or-none release of hemoglobin by the rupture of RBCs into account, providing new insight into the polymer-induced hemolysis regarding how individual or collective cells respond to the polymers.

Key words： Hemolysis Antimicrobial polymer Amphiphilic polymethacrylate Kinetic analysis Membrane disruption

Received: 13 November 2014 Published: 07 February 2015

Fund:

This research was supported by the Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, NSF CAREER Award (No. DMR-0845592 to KK), and JSPS KAKENHI, Grant-in-Aids for Challenging Exploratory Research (No. 25650053) for Young Scientists (Nos. 24681028 and 22700494 to KY). We thank Professor Robertson Davenport at the University of Michigan Hospital for supplying the red blood cells. We also thank Professor Edmund F. Palermo at Rensselaer Polytechnic Institute for his valuable discussions and comments.

Corresponding Authors: Kazuma Yasuhara, Kenichi Kuroda E-mail: yasuhara@ms.naist.jp;kkuroda@umich.edu

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http://www.chinchemlett.com.cn/EN/10.1016/j.cclet.2015.01.029 OR http://www.chinchemlett.com.cn/EN/Y2015/V26/I04/479

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