The relationship between the temperature-sensitivity of the release of an entrapped drug from liposome as well as the type of drug or liposome is discussed. The drug release from DPPC liposome (dipalmitoylphosphatidylcholine liposome) has been confirmed to increase abruptly near its phase-transition temperature for both low-molecular-weight compouds (such as calcein) and high-molecular-weight compounds (such as dextran). The amount of temperature-sensitive calcein released from the liposomes was dependent on the method of liposome preparation: that is, the release from REV (reverse phase evaporated vesicle) was the highest; next was that from LUV (large unilamellar vesicle prepered by detergent removal method), and lowest was from SUV (small unilamellar vesicle prepared by an ultrasonication method). In order to examine the size effect of liposomes on temperature-sensitive drug release, REV was fractionated into three groups according to their average sizes and calcein release for each group was investigated. The temperature at which calcein release showed a maximum was almost the same in each of three groups; while as the average liposome size of a group was larger, the initial rate of calcein release became higher and the temperature at which calcein release began became lower. The amount of release of a entrapped drug was primarily dependent on the molecular weight of the drug, in spite of the variety of drugs investigated.
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