目的 考察壳聚糖修饰的L-天门冬酰胺酶脂质体的血浆稳定性及药动学特性。方法 血浆稳定性:于不同时间点,分别测定L-天门冬酰胺酶和壳聚糖修饰的L-天门冬酰胺酶脂质体在大鼠空白血浆中的活性。大鼠静脉注射L-天门冬酰胺酶和壳聚糖修饰的L-天门冬酰胺酶脂质体后,分别考察其药动学特性。采用DAS药动学软件计算药动学参数。结果 在空白血浆中,壳聚糖修饰的L-天门冬酰胺酶脂质体的活性高于L-天门冬酰胺酶;壳聚糖修饰的L-天门冬酰胺酶脂质体的活性-时间曲线下面积(AUC0-48 h)约为L-天门冬酰胺酶的3.3倍,壳聚糖修饰的L-天门冬酰胺酶脂质体的平均滞留时间(MRT0-48 h)约为ASP的2.3倍。结论 壳聚糖修饰的L-天门冬酰胺酶脂质体能提高L-天门冬酰胺酶的血浆稳定性及生物利用度。
Abstract
OBJECTIVE To investigate the stability and pharmacokinetics of chitosan-modified L-asparaginase liposomes. METHODS The activities of L-asparaginase and chitosan-modified L-asparaginase liposomes in blank rat plasma were determined at different time. L-asparaginase and chitosan-modified L-asparaginase liposomes were intravenously injected to rats through tail vein. The pharmacokinetic parameters were calculated by DAS. RESULTS The activity of chitosan-modified L-asparaginase liposomes in plasma was significantly higher than that of L-asparaginase. The AUC0-48 hof chitosan-modified L-asparaginase liposomes was as 3.3 times as that of L-asparaginase. And the MRT0-48 hof chitosan-modified L-asparaginase liposomes was as 2.3 times as that of L-asparaginase. CONCLUSION Chitosan-modified L-asparaginase liposomes can improve the stability and bioavailability of L-asparaginase.
关键词
L-天门冬酰胺酶 /
壳聚糖 /
脂质体 /
稳定性 /
药动学
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Key words
L-asparaginase /
chitosan /
liposome /
stability /
pharmacokinetics
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中图分类号：
R944
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参考文献
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