Rapid leakage from PEGylated liposomes triggered by bubbles.

Liposomes are applicable to fabrication of colloidal carriers of drugs and proteins. Physicochemical stimuli-triggered leakage from liposomes offers a wide variety of applications in biochemical and biomedical fields. In this work, effects of bubbles on the characteristics of PEGylated liposomes encapsulating 5(6)-carboxyfluorescein were examined. The liposomes were composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1-10 mol% 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated with poly(ethylene glycol) (DSPE-PEG). The mean molecular mass Mr,PEG of the PEG moiety was 550 or 5000. A bubble column was used for generating air bubbles at a superficial gas velocity of 0.58-0.88 cm s-1. Leakage from the PEGylated liposomes was remarkably accelerated at 25 or 40 °C by introducing air to a liposome suspension at pH 7.4, whereas the dye molecules practically remained encapsulated in the liposomes being suspended in static liquid. The apparent rate constant for the dye release from the liposomes composed of DOPC and 1 mol% DSPE-PEG (Mr,PEG = 5000) being suspended in the gas-liquid flow was 168 times larger than that obtained with respect to the same liposomes in static liquid. Leakage from non-PEGylated liposomes was not pronounced even in the gas-liquid flow. Furthermore, the release rate of the dye from the PEGylated liposomes in liquid shear flow (no bubble) was clearly smaller than that in the gas-liquid flow, meaning that the interaction between bubbles and the liposomes was responsible for the observed rapid leakage. Adsorption of the PEGylated lipids to bubbles was indicated to induce leaky lipid bilayers, which was discussed on the basis of the conformational state of the PEG moiety.