Wu N Z, Braun R D, Gaber M H, Lin G M, Ong E T, Shan S, Papahadjopoulos D, Dewhirst M W
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Microcirculation. 1997 Mar;4(1):83-101. doi: 10.3109/10739689709148320.
The success of liposome-based drug delivery systems for tumor targeting relies on maximum extravasation of liposomes into tumor interstitium, as well as optimal release of contents from the liposomes once within the tumor Liposome extravasation and content release are two separate processes that can be individually or jointly manipulated so a method is needed to monitor these two processes independently and simultaneously. In this report, we describe a method to measure liposome extravasation and content release in tumor tissues growing in a rat skinfold window chamber preparation.
Mixtures of liposomes containing either doxorubicin or calcein, both of which are fluorescent, and liposomes surface-labeled with rhodamine were injected intravenously. Fluorescent, light intensities in a tumor region in two fluorescent channels were measured using an image-processing system. Light intensities of plasma from blood samples were also measured using this system. These measurements were used to calculate the amounts of liposomes and released contents in both plasma and tumor interstitium. The calculations were based on the fact that the liposome surface labels and contents emit fluorescent light at different wavelengths and when encapsulated, the contents fluorescence is self-quenched. The model included equations to account for fluorescent light "cross-contamination" by the two fluorochromes as well as equations relating the measured fluorescent light intensities to the amounts of liposomes and released contents. This method was applied to three situations in which liposome extravasation and content release were manipulated in different, predictable ways.
Our results indicate that this method can perform simultaneous independent and quantitative measurements of liposome extravasation and content release. This method can potentially be used to study drug delivery of other carrier systems in vivo.
基于脂质体的肿瘤靶向给药系统的成功依赖于脂质体最大限度地渗入肿瘤间质，以及脂质体进入肿瘤后内容物的最佳释放。脂质体的渗出和内容物释放是两个独立的过程，可以单独或联合控制，因此需要一种方法来独立且同时监测这两个过程。在本报告中，我们描述了一种在大鼠皮肤褶窗小室制备中生长的肿瘤组织中测量脂质体渗出和内容物释放的方法。
静脉注射含有阿霉素或钙黄绿素（两者均为荧光物质）的脂质体混合物，以及用罗丹明进行表面标记的脂质体。使用图像处理系统测量两个荧光通道中肿瘤区域的荧光光强度。还使用该系统测量血样中血浆的光强度。这些测量用于计算血浆和肿瘤间质中脂质体和释放内容物的量。计算基于这样一个事实，即脂质体表面标记物和内容物在不同波长下发出荧光光信号，并且当被包裹时，内容物的荧光会发生自猝灭。该模型包括用于解释两种荧光染料引起的荧光光“交叉污染”的方程，以及将测量的荧光光强度与脂质体和释放内容物的量相关联的方程。该方法应用于三种情况，其中脂质体渗出和内容物释放在不同的、可预测的方式下进行控制。
我们的结果表明，该方法可以同时独立且定量地测量脂质体渗出和内容物释放。该方法有可能用于研究体内其他载体系统的药物递送。
