Use of avidin/biotin-liposome system for enhanced peritoneal drug delivery in an ovarian cancer model.
Use of avidin/biotin-liposome system for enhanced peritoneal drug delivery in an ovarian cancer model.
复制标题
使用抗生物素蛋白/生物素-脂质体系统增强卵巢癌模型中的腹膜药物递送。
DOI：
10.1016/j.ijpharm.2007.01.010
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发表时间：
2007
影响因子：
5.8
通讯作者：
Goins,BethA
中科院分区：
文献类型：
--
作者：
Zavaleta,CristinaL;Phillips,WilliamT;Soundararajan,Anuradha;Goins,BethA
本研究的目的是确定抗生物素蛋白/生物素-脂质体系统在卵巢癌异种移植模型中的分布。确定了最佳亲和素/生物素-脂质体注射顺序，增强脂质体向腹膜的积聚。NIH：OVCAR-3细胞接种后2周，将大鼠分为3组。第1组（B-A）（n=4）在腹腔注射亲和素前30 min腹腔注射99 mTc-蓝-生物素-脂质体。第2组（A-B组），腹腔注射抗生物素蛋白30 min后腹腔注射99 mTc-蓝-生物素-脂质体。第3组（A-B 2 h）（n=5），腹腔注射抗生物素蛋白2 h后再腹腔注射99 mTc-蓝-生物素-脂质体。每组中另外三只非肿瘤裸大鼠作为对照，并接受相同的注射顺序。在注射99 mTc-蓝-生物素-脂质体后的不同时间开始闪烁成像。成像后，在脂质体注射后23小时对大鼠实施安乐死以进行组织生物分布。图像显示对照和肿瘤动物之间的脂质体分布没有明显差异。肿瘤大鼠4 h区域摄取分析显示A-B 2 h组淋巴通道摄取显著增加（p<0.05），A-B组腹膜摄取有增加的趋势。到22小时，所有组的腹膜和淋巴通道摄取相似。尸检时，大部分活性见于蓝色网膜、隔膜、纵隔和腹部淋巴结。肠道活动很小。这些结果与之前的正常大鼠研究相关，并证明了这种抗生物素蛋白/生物素-脂质体系统在该卵巢癌异种移植模型中延长药物向腹膜腔和相关淋巴结递送的潜在用途。
The goal of this study was to determine the distribution of the avidin/biotin-liposome system in an ovarian cancer xenograft model. Optimal avidin/biotin-liposome injection sequence with enhanced liposome accumulation to the peritoneum was determined. Two weeks after NIH:OVCAR-3 cell inoculation, rats were divided into three groups. Group 1 (B-A) (n=4), received an intraperitoneal injection of99mTc-blue-biotin-liposomes 30min before an intraperitoneal injection of avidin. Group 2 (A-B) (n=4), received an intraperitoneal injection of avidin 30min before an intraperitoneal injection of99mTc-blue-biotin-liposomes. Group 3 (A-B 2h) (n=5), received an intraperitoneal injection of avidin 2h before an intraperitoneal injection of99mTc-blue-biotin-liposomes. Three additional non-tumor nude rats served as controls in each group, and were subjected to the same injection sequences. Scintigraphic imaging commenced at various times post99mTc-blue-biotin-liposome injection. After imaging, rats were euthanized at 23h post-liposome injection for tissue biodistribution. Images showed no apparent difference in liposome distribution between control and tumor animals. Regional uptake analysis at 4h for tumor rats showed significantly higher lymphatic channel uptake in the A-B 2h group (p<0.05) and a trend of increased peritoneal uptake in A-B group. By 22h, peritoneal and lymphatic channel uptake was similar for all groups. At necropsy, most activity was found in blue-stained omentum, diaphragm, mediastinal and abdominal nodes. Bowel activity was minimal. These results correlate with previous normal rat studies, and demonstrate potential use of this avidin/biotin-liposome system for prolonging drug delivery to the peritoneal cavity and associating lymph nodes in this ovarian cancer xenograft model.