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Phase transition-induced rapid permeabilization of liposome membranes composed of milk-sphingomyelin



Milk-sphingomyelin (SPM) liposomes encapsulating 5(6)-carboxyfluorescein (CF) were prepared and characterized in terms of the temperature-dependent permeability of the SPM membrane. The liposomes were monodisperse and 109 nm in mean diameter. The SPM membrane was highly permeable to CF when the temperature rapidly increases toward 35°C, exhibiting apparent permeability coefficient of 1.88 × 10−8 cm/s. The size distribution of SPM liposomes was practically unchanged at 35°C. In clear contrast, the membrane was barely permeable at lower and higher temperatures than 30–35°C. The fluorescence polarization measurement, which was performed to evaluate the membrane fluidity, indicated that the rapid membrane permeabilization of SPM liposomes was induced by its phase transition. The temperature-dependent change in the SPM membrane fluidity was much smaller than that in the membrane composed of 1-myristoyl-2-palmitoyl-sn-glycero-3-phosphocholine (MPPC) or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), which had comparable acyl chain properties to one of the constituents of SPM. Thus, the SPM liposomes possesses unique features that make their membrane highly permeable at the specific temperature range with moderate change in the membrane fluidity.

Practical applications: Kinetically fast permeabilization of SPM liposomes at a near physiological temperature of 35°C is a phenomenon applicable to temperature-sensitive rapid release of cosmetic compounds from the biocompatible SPM liposomes. Furthermore, the reactions catalyzed by liposome-encapsulated enzymes, which have been utilized as drugs and biosensors, would be controlled using the SPM liposomes based on the permeability of substrates without causing thermal deactivation of enzymes.