Thermosensitive liposomes: Extravasation and release of contents in tumor microvascular networks
Thermosensitive liposomes: Extravasation and release of contents in tumor microvascular networks
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DOI：
10.1016/s0360-3016(96)00389-6
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发表时间：
1996-12-01
影响因子：
7
通讯作者：
Papahadjopoulos, D
中科院分区：
文献类型：
--
作者：
Gaber, MH;Wu, NZ;Papahadjopoulos, D
目的：研究热暴露是否会加速药物从热敏性固体稳定型脂质体中的释放，并增强其在肿瘤组织中的外渗。材料和方法：在限定的温度条件下(34度、42度和45℃)，用荧光视频显微镜测量脂质体在大鼠皮瓣窗腔内的渗出和内容物的释放，并通过SIT摄像机记录包含多条血管的组织区域的图像。注射两组具有相同脂质成分的脂质体：一种脂质体制剂表面标记有罗丹明-PE(Rh-PE)，另一种脂质体制剂含有自猝灭浓度的阿霉素(Dox)或钙黄素(Calcein)，在34℃(皮肤的生理温度)下测量整个组织区域的光强度1小时，在42℃或45℃下2小时，然后使用这些测量来计算血管内和间质区域内每个示踪剂(脂质体表面标记和释放的内容物)产生的荧光强度，结果：温敏脂质体在间质中的Rh-PE计算强度(代表渗出的脂体量)在1小时内较低，当温度保持在34℃并增加到加热前的47倍时，当肿瘤在42℃或45℃加热1h时，间质中脂质体内容物(Dox)的计算强度可以忽略不计，而当肿瘤分别在42℃和45℃加热1h时，计算的间质中脂质体内容物(Dox)的强度分别增加了38和76倍，而将Calcein包裹在脂质体中而不是Dox时，得到了类似的值。非温敏性脂质体也有类似的外渗增加，但当窗口加热到45℃1h时，Dox的释放几乎可以忽略不计，停止加热后脂质体继续外溢，但在去热后停止内容物释放，如果在脂质体给药24 h后加热，也可以看到渗出的脂质体释放Dox，但在这种情况下没有进一步增加脂质体的外渗，结论：我们的数据表明，加温可以选择性地提高药物从热敏性脂质体到靶组织的释放量和释放率。版权所有(C)1996爱思唯尔科学公司。
Purpose: The purpose of this study was to determine whether hyperthermic exposure would accelerate drug release from thermosensitive sterically stabilized liposomes and enhance their extravasation in tumor tissues,Materials and Methods: In vivo fluorescence video microscopy was used to measure the extravasation of liposomes, as well as release of their contents, in a rat skin flap window chamber containing a vascularized mammary adenocarcinoma under defined thermal conditions (34 degrees, 42 degrees, and 45 degrees C), Images of tissue areas containing multiple blood vessels were recorded via a SIT camera immediately before, and for up to 2 h after i,v, injection of two liposome populations with identical lipid composition: one liposome preparation was surface labeled with Rhodamine-PE (Rh-PE) and the other contained either Doxorubicin (Dox) or calcein at self-quenching concentrations, The light intensity of the entire tissue area was measured at 34 degrees C (the physiological temperature of the skin) for 1 h, and at 42 degrees or 45 degrees C for a second hour, These measurements were then used to calculate the fluorescent light intensity arising from each tracer (liposome surface label and the released contents) inside the vessel and in the interstitial region,Results: The calculated intensity of Rh-PE for the thermosensitive liposomes in the interstitial space (which represents the amount of extravasated liposomes) was low during the first hour, while temperature was maintained at 34 degrees C and increased to 47 times its level before heating, when the tumor was heated at 42 degrees or 45 degrees C for 1 h, The calculated intensity of the liposome contents (Dox) in the interstitial space was negligible at 34 degrees C, and increased by 38- and 76-fold, when the tumor was heated at 42 degrees and 45 degrees C for 1 h, respectively, Similar values were obtained when calcein was encapsulated in liposomes instead of Dox, A similar increase in liposome extravasation was seen with nonthermosensitive liposomes, but negligible release of Dox occurred when the window chamber was heated to 45 degrees C for 1 h, Extravasation of liposomes continued after heating was stopped, but content release stopped after removal of heat, Release of Dox from extravasated liposomes was also seen if heating was applied 24 h after liposome administration, but no further enhancement of liposome extravasation occurred in this case,Conclusions: Our data suggest that hyperthermia can be used to selectively enhance both the delivery and the rate of release of drugs from thermosensitive Liposomes to targeted tissues. Copyright (C) 1996 Elsevier Science Inc.