Polymer-protected liposomes: Association of hydrophobically-modified PEG with liposomes

We demonstrate the impact of cooperative interactions on liposome protection by incorporating multiple hydrophobic sites on poly(ethylene glycol) (PEG) polymers. Our hydrophobically-modified PEGs (HMPEGs) are comb-graft copolymers with precisely alternating, monodisperse PEG blocks (MW= 6, 12, or 35 kDa), bonded to C18 stearylamide hydrophobes. Cooperativity is controlled by varying the extent of oligomerization at a constant ratio of PEG to stearlyamide. The association of polymer with liposomes increases with the degree of oligomerization; equilibrium constants for 6 kDa PEG increases from 6.1 +/- 0.8 (mg/m(2))/(mg/ml) for 3 loops to 78.1 +/- 12.2 (mg/m(2))/(mg/ml) for 13 loops. In addition, HMPEG6k-DP3 (with three 6 kDa loops) results in superior, irreversible protection from complement protein binding than DSPE-PEG5k after 12 hours.