Lipid Membrane Binding and Cell Protection Efficacy of Poly(1,2-butylene oxide)-b-poly(ethylene oxide) Copolymers

Poloxamers consisting of poly(ethylene oxide) (PEO) and poly(propylene oxide) segments can protect cell membranes against various forms of stress. We investigated the role of the hydrophobic block chemistry on polymer/membrane binding and cell membrane protection by comparing a series of poly(butylene oxide)-b-PEO (PBO-b-PEO) copolymers to poloxamer analogues, using a combination of pulsed-field-gradient (PFG) NMR experiments and a lactate dehydrogenase (LDH) cell assay. We found that the more hydrophobic PBO-b-PEO copolymers bound more significantly to model liposomes composed of 1-palmitol-2-oleoyl-glycero-3-phosphocholine (POPC) compared to poly(propylene oxide) (PPO)/PEO copolymers. However, both classes of polymers performed similarly when compared by an LDH assay. These results present an important comparison between polymers with similar structures but with different binding affinities. They also provide mechanistic insight as enhanced polymer/lipid membrane binding did not directly translate to increased cell protection in the LDH assay, and therefore, additional factors need to be considered when trying to achieve greater membrane protection efficacy.