Morphological transition of amphiphilic block copolymer/PEGylated phospholipid complexes induced by the dynamic subtle balance interactions in the self-assembled aggregates

Recently, there has been an increasing interest in the control of morphological transition of block copolymer aggregates. Here, we report how to control the morphological transition of methoxy polyethylene glycol-poly(D,L-lactic acid) (PDLLA-MPEG) by adding 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] (DSPE-PEG). In the aggregates formed by dialyzing DSPEPEG/PDLLA-MPEG mixed solutions against water, the two hydrophobic fatty acid tails of DSPE-PEG will preferentially anchor to the hydrophobic segment end of PDLLA-MPEG by interdigitating between these two tails and PDLLA segments. Consequently, DSPE-PEG and PDLLA-MPEG will form "ABA" temporary supra-amphiphiles in which A represents a poly(ethylene glycol) (PEG) chain segment and B is a mixed hydrophobic segment composed of PDLLA and DSPE segments; the repulsive force derived from the PEG segments of DSPE-PEG can affect the stability of "ABA" temporary supra-amphiphiles. Our results show that the dynamic subtle balance between the number of "ABA" temporary supra-amphiphiles formed and the strength of repulsive force between the PEG segments of DSPE-PEG drives the morphological structure of DSPE-PEG/PDLLA-MPEG aggregates to change from micelles to vesicles, then to semi-vesicles and finally to mixed micelles, with increasing DSPE-PEG additions.