Disruption of Lipid Membrane Integrity by Synthetic Water-Soluble Polymers: Effects of Lipid Headgroup

Water-soluble polymers (WSPs) represent a key class of polymers widely employed in liquid formulations across diverse industries. We investigated their interactions with synthetic lipid membranes, as well as cytotoxicity triggered by membrane disruption. Zwitterionic 1,2-dioleoyl-<i>sn</i>-glycero-3-phosphocholine (DOPC) and negatively charged 1,2-dioleoyl-<i>sn</i>-glycero-3-phosphoglycerol (DOPG) liposomes were utilized as lipid membrane models for assessing fluorescence leakage caused by two positively charged, two negatively charged, and one neutral WSPs. Positively charged WSPs induced substantial leakage in DOPG liposomes with increasing polymer concentrations, whereas the negatively charged WSP caused only minor leakage in DOPC liposomes at high concentrations, and nonionic WSPs did not cause significant disruption. Quantification of in vitro cytotoxicity on one human (MCF7) and one fish (RTgill-W1 from <i>Oncorhynchus mykiss</i>) cell line confirmed the WSP's ability to disrupt membrane integrity. Cationic WSPs also caused cytotoxicity in both cell lines at similar concentrations, distinguishing them from negatively charged and neutral WSPs. These findings highlight the pivotal role of electrostatic interactions between charge characteristics of WSPs and phospholipid headgroups of biological membranes. Although WSPs are often exempted for toxicity tests in chemicals regulations such as the European Union's REACH, further evaluation is necessary to understand their toxic potential and modes of toxic action.