Application of Synthetic Alkyl Glycoside Vesicles as Drug Carriers. III. : Plasma Components Affecting Stability of the Vesicles

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Long-chain alkyl glycosides form liposome-like vesicles. However, they are unstable in plasma and thus are unsuitable as drug carriers. The mechanisms causing the instability of palmitoyl glucoside vesicles (Glu-liposomes) in plasma were investigated in this study. They very rapidly released about 70% of their aqueous content at the start of incubation with fresh rat plasma at 37℃. On the other hand, phosphatidylcholine liposomes (PC-liposomes) released about 30% of their content, though the release pattern was very similar. Two components were suspected to b involved in destabilizing the Glu-liposomes in plasma from a plasma dilution experiment, and their effects seemed to depend on the type or size of the vesicles. The activity disappeared on pre-heating of the plasma at 56℃ for 30 min in the case of PC-liposomes, but not Glu-liposomes, and about 35% of the contents of the latter was still released on incubation even with pre-heated plasma. This result indicates that the activity destabilizing glycoside vesicles in plasma was composed of two factors, one heat-stable and the other heat-labile. The heat-stable one was consumed by incubation with empty glycoside vesicles, regardless of the sugar moiety or size of vesicles, but not by PC-liposomes. Therefore, the heat-stable factor seemed to be specific to vesicles covered with sugar moieties. By fractionation of plasma protein by the salting-out technique, the activity was found in the albumin fraction.
公益社団法人日本薬学会の論文
1988-05-25

Application of Synthetic Alkyl Glycoside Vesicles as Drug Carriers. III. : Plasma Components Affecting Stability of the Vesicles

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