Targeted and sustained drug delivery using PEGylated galactosylated liposomes
Targeted and sustained drug delivery using PEGylated galactosylated liposomes
复制标题
DOI：
10.1016/s0378-5173(03)00383-1
复制
发表时间：
2003-11-06
影响因子：
5.8
通讯作者：
Hashida, M
中科院分区：
文献类型：
--
作者：
Managit, C;Kawakami, S;Hashida, M
为了实现脂质体向肝实质细胞（PC）的持续和靶向递送，我们用半乳糖基化胆固醇衍生物（Gal-C4-Chol）和聚山梨酯（Tween）20或1，2-二硬脂酰-sn-甘油基-3-磷酸乙醇胺-N-聚乙二醇（PEG，-DSPE）修饰二硬脂酰-L-磷脂酰胆碱（DSPC）/胆固醇（Chol）（60：40）（DSPC/Chol）脂质体。静脉注射后，DSPC/Chol/Gal-C4-Chol（60：35：5）（Gal）脂质体从血液循环中迅速消除，大部分在肝脏中回收。与Gal-脂质体相比，DSPC/Chol/Gal-C4-Chol/Tween 20（55：35：5：5）（Tween 20-Gal）脂质体的血液消除略微降低。相比之下，使用DSPC/Chol/Gal-C4-Chol/PEG（2000）-DSPE（59：35：5：1）（PEG（2000）-Gal）脂质体观察到血液消除显著降低。DSPC/Chol/Gal-C4-Chol/PEG（350）-DSPE（59：35：5：1）（PEG（350）-Gal）脂质体的肝摄取介于PEG（2000）-Gal-脂质体和Tween 20-Gal-脂质体之间。肝PC对PEG（350）-Gal-脂质体的摄取是非实质细胞（NPC）的7.7倍。这些结果表明PEG（350）-DSPE可以控制半乳糖脂质体对肝PC的递送速率而不丧失其靶向能力。(C)2003 Elsevier B. V.保留所有权利。
To achieve a sustained and targeted delivery of liposomes to liver parenchymal cells (PC), we modified distearoyl-L-phosphatidylcholine (DSPC)/cholesterol (Chol) (60:40) (DSPC/Chol) liposomes with a galactosylated cholesterol derivative (Gal-C4-Chol), and polysorbate (Tween) 20 or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-polyethylene glycol (PEG,-DSPE). After intravenous injection, DSPC/Chol/Gal-C4-Chol (60:35:5) (Gal) liposomes were rapidly eliminated from the blood circulation and mostly recovered in the liver. The blood elimination of DSPC/Chol/Gal-C4-Chol/Tween 20 (55:35:5:5) (Tween 20-Gal) liposomes was slightly reduced as compared to Gal-liposomes. In contrast, a significant reduction in the blood elimination was observed with DSPC/Chol/Gal-C4-Chol/PEG(2000)-DSPE (59:35:5:1) (PEG(2000)-Gal) liposomes. Hepatic uptake of DSPC/Chol/Gal-C4-Chol/PEG(350)-DSPE (59:35:5:1) (PEG(350)-Gal) liposomes was intermediate between PEG(2000)-Gal-liposomes and Tween 20-Gal-liposomes. The uptake of PEG(350)-Gal-liposomes by liver PC was 7.7-fold higher than that by non-parenchymal cells (NPC). These results suggest that PEG(350)-DSPE can control the delivery rate of Gal-liposomes to liver PC without losing its targeting capability. (C) 2003 Elsevier B.V. All rights reserved.