Chemistry tmd Physics o f Lipids, 34 (1984) 245-256 245 Elsevier Scientific Publishers Ireland Ltd. TEMPERATURE-DEPENDENT PERMEABILITY OF LARGE UNILAMELLAR LIPOSOMES RICHARD L. MAGINand MICHAEL R. NIESMAN Bioacoustics Research Laboratory Department o f Electrical Engineering University of Illinois Urbana, IL 61801 {U.S.A.) Received October 15th, 1 9 8 3 accepted November l lth, 1983 The temperature-dependent drug leakage from liposomes composed of dipalmitoylphos- phatidylcholine and dipalmitoylphosphatidylglycerol (4:1, by weight) was studied. Experi- ments were performed in Hepes buffer and 50% fetal calf serum. Large unilamellar liposomes were formed by the reverse phase evaporation process and extruded through a series of poly- carbonate membranes with pore sizes of 0.4, 0.2, 0.1 and 0.08/~m. The release of the water soluble radioisotopes cytosine 1-#-D-[3H]arabinofuranoside and [3H]inulin from the aqueous compartment of these liposomes was measured as a function of time and temperature. Both radioisotopes were released at temperatures near 42°C, the solid-to-liquid-crystalline phase transition temperature of these lipids. The percent drug release decreased as the size of the liposomes was reduced. This effect was more pronounced in Hepes buffer than serum. The release of both radioisotopes was greatest at 40"C in Hepes buffer and at 43°C in 50% fetal calf serum. In addition, the rate of drug release was much faster in serum than in buffer. These results suggest that different drug release processes are occurring in buffer and in serum. Key words: liposome; temperature; drug release; inulin; permeability; cytosine arabinofurano- side. Introduction The permeability properties of liposomes are important for understanding the function of biological membranes and for designing liposomes as selective drug delivery vehicles. Previous investigations of liposome permeability have dealt mainly with multflamellar vesicles (MLV) and small unilamellar vesicles (SUV) [1-8]. Those experiments showed that liposomes are highly permeable to water, anions, cations, carboxyfluorescein, glucose and sucrose near the solid-to-liquid- crystalline phase transition temperature (Tin) of the component lipids. The increase in permeability observed near T m depends upon the molecular size of the substance under study and the phospholipid composition of the liposome membrane. In general, permeability near T m decreases with an increase in the diameter of the permeating ion, or the length of the phospholipid's fatty acyl side chain. The theoretical interpretation of this behavior involves the formation of small pores in the membrane at regions where the solid and liquid-crystalline phases are in contact [6]. 0009-3084/84/$03.00 © 1984 Elsevier Scientific Publishers Ireland Ltd, Published and Printed in Ireland