Self-association of zwitterionic polymer-lipid conjugates in water as examined by scattering measurements.

As a model of lipopeptide, a zwitterionic polymer-lipid conjugate was prepared from carboxymethylbetaine monomer (CMB) using a lipophilic initiator having a cholesteryl or dihexadecylglyceryl end group for atom transfer radical polymerization (ATRP). The polymer-lipid conjugates (Lipid-PCMB) obtained could be dispersed in water, and self-association of the compounds could be characterized by both light scattering (dynamic light scattering, DLS; electrophoretic light scattering, ELS) and small-angle X-ray scattering (SAXS). DLS and ELS measurements showed no secondary aggregation of the self-associated Lipid-PCMB molecules in salt solutions, though their surfaces were almost charge-balanced. The hydrophilic PCMB layer of Lipid-PCMB aggregates gave rise to dispersions under ionic conditions. Furthermore, structural analyses by DLS, ELS and SAXS measurements suggested that Lipid-PCMB aggregates consisted of a hydrophobic lipid core and a hydrophilic PCMB layer, that is, a core-shell structure. To the best our knowledge, this is the first study in which SAXS analyses were performed for zwitterionic polymer-lipid conjugates.