Application of synthetic alkyl glycoside vesicles as drug carriers. III. Plasma components affecting stability of the vesicles.
Application of synthetic alkyl glycoside vesicles as drug carriers. III. Plasma components affecting stability of the vesicles.
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合成烷基糖苷囊泡作为药物载体的应用
DOI：
10.1248/cpb.36.1841
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发表时间：
1988
影响因子：
1.7
通讯作者：
Y. Kato
中科院分区：
文献类型：
--
作者：
H. Kiwada;I. Nakajima;H. Matsuura;M. Tsuji;Y. Kato
长链烷基糖苷形成脂质体样囊泡。然而，它们在血浆中不稳定，因此不适合作为药物载体。本研究探讨了血浆中棕榈酰葡萄糖苷囊泡（脂质体）不稳定的机制。在37°C下与新鲜大鼠血浆孵育开始时，它们非常迅速地释放了约70%的水含量。另一方面，磷脂酰胆碱脂质体（pc -脂质体）的释放量约为其含量的30%，但释放模式非常相似。在血浆稀释实验中，有两种成分被怀疑参与破坏血浆中葡脂质体的稳定，它们的作用似乎取决于囊泡的类型或大小。pc -脂质体在56℃下预热30 min后活性消失，而葡聚糖脂质体则没有，葡聚糖脂质体在预热后的培养过程中仍有35%左右的内容物释放。这表明血浆中糖苷囊泡的失稳活性由热稳定和热不稳定两个因素组成。与空糖苷囊泡孵育消耗热稳定的一种，无论糖的部分或囊泡的大小，但不使用pc脂质体。因此，热稳定因子似乎是特定于被糖部分覆盖的囊泡。用盐析技术分离血浆蛋白，发现白蛋白部分有活性。
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°C. 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°C 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.