Development of Model Diblock Copolymer Surfactants for Mechanistic Investigations of Cell Membrane Stabilization

Abstract

Amphiphilic triblock copolymers of poly(ethylene oxide) and poly(propylene oxide), generically referred to as poloxamers, have been identified for therapeutic use in cell membrane stabilization applications since the early 1990s. Historically, mechanistic investigations of block copolymer facilitated membrane stabilization have nearly exclusively featured poloxamers, commercially available in a wide range of molecular weights and hydrophobic/hydrophilic compositions. This work instead considers diblock copolymers of poly(ethylene oxide) and poly(propylene oxide), for which molecular properties can be easily tuned by living anionic polymerization. The diblock architecture simplifies the structure-function understanding of block copolymer interactions with membranes by eliminating a redundant hydrophilic block (A) from the poloxamer A-B-A architecture. Work presented here indicates that these diblock copolymers are capable of shielding liposome model membranes from harmful free radical-initiated peroxidation at lower loadings than analogous triblock copolymers. Besides the pharmacological advantages of lower required doses, the finding highlights the significance with respect to membrane interaction of differences in the chemical environments of the hydrophobic blocks between the triblock and diblock architectures. From this point, the roles of both hydrophobic block length and end-functionality were explored in liposome and in vitro model stresses, and the dependence of therapeutic benefit on each was established. Future systems to consider are discussed, and additional methods for investigation are detailed.