A novel approach for the increased delivery of pharmaceutical agents to peritoneum and associated lymph nodes
A novel approach for the increased delivery of pharmaceutical agents to peritoneum and associated lymph nodes
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DOI：
10.1124/jpet.102.037119
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发表时间：
2002-10-01
影响因子：
3.5
通讯作者：
Goins, B
中科院分区：
文献类型：
--
作者：
Phillips, WT;Medina, LA;Goins, B
描述了一种新的方法来延长脂质体在腹膜中的滞留，同时增加脂质体在引流腹膜的淋巴结中的沉积。将包裹蓝色染料的等量(1ml)~(99m)Tc-生物素-脂质体注入大鼠腹膜内。给药30min后，5只大鼠(实验组)腹腔注射亲和素(5 Mg)，其余5只大鼠作为对照组。在注射脂质体后1小时和24小时采集放射性核素图像，然后进行组织生物分布研究。24小时的图像清楚地显示了实验动物和对照动物之间非常不同的分布。在实验大鼠中，大部分活动在腹部以及腹部和纵隔淋巴结中可见。对照组血液中注射剂量百分比(%ID)显著高于实验组(14.0±-1.7vs0.17+/-0.03%，P<；0.001)。对照组(23.3+/-3.9%)显著高于实验组(0.78+/-0.8%；P=0.001)。在实验动物的腹部蓝染结节(4.7%)和纵隔结节(2.3%)中检测到显著的~(99m)Tc活性，而在对照组动物中未检测到蓝染结节。本研究中描述的腹膜内生物素-脂质体/亲和素递送系统可能用于将脂质体包裹的药物递送到在腹膜中扩散的疾病过程，如转移性卵巢癌、胃癌和结直肠癌，以及感染性腹膜炎。
A novel method for prolonging the retention of liposomes in the peritoneum while increasing liposome deposition in lymph nodes that drain the peritoneum is described. An aliquot (1 ml) of technetium-99m (Tc-99m)-biotin-liposomes encapsulating blue dye was injected intraperitoneally in rats. Thirty minutes after administration of the Tc-99m-blue-biotin-liposomes, five rats (experimental) were administered avidin (5 mg) intraperitoneally, whereas the remaining five rats served as controls. Scintigraphic images were acquired at baseline and 1 and 24 h after the liposome injection followed by a tissue biodistribution study. Images at 24 h clearly demonstrated very different distributions between the experimental and control animals. In experimental rats, most of the activity was visualized in the abdominal region, and in abdominal and mediastinal lymph nodes. The percentage of the injected dose (% ID) in the blood was significantly higher in the control group than in the experimental group (14.0 +/- 1.7 versus 0.17 +/- 0.03%; P < 0.001). The % ID in the spleen was also significantly greater for controls (23.3 +/- 3.9%) compared with the experimental group (0.78 +/- 0.8%; P = 0.001). Significant Tc-99m activity was detected in blue-stained abdominal nodes (4.7%) and mediastinal nodes (2.3%) from the experimental animals, whereas no blue-stained nodes were detectable in the control animals. The intraperitoneal biotin-liposome/avidin delivery system described in this study could potentially be used for delivery of liposome-encapsulated drugs to disease processes that become disseminated in the peritoneum such as metastatic ovarian, gastric, and colorectal cancer, as well as infectious peritonitis.