Syrigos Konstantinos N, Vile Richard G, Peters A Michael, Harrington Kevin J
Cancer Research UK Targeted Therapy Laboratory, Centre for Cell and Molecular Biology, Institute of Cancer Research, London, UK.
Acta Oncol. 2003;42(2):147-53. doi: 10.1080/02841860310005697.
The biodistribution and pharmacokinetics of 111In-DTPA-labelled pegylated liposomes (IDLPL) and unencapsulated 111In-DTPA administered by the intraperitoneal (i.p.) and i.v. routes in non-tumour-bearing mice were compared. Mice received i.p. or i.v. injections of 0.37 MBq 111In-DTPA either encapsulated in liposomes or as an unencapsulated agent. A variety of tissues were dissected from 5 min to 192 h to determine the biodistribution and pharmacokinetics. Injection of IDLPL via the i.p. route caused a 74-fold increase in the area under the concentration (AUC) versus time curve in the peritoneum compared to unencapsulated 111In-DTPA. Similarly, the AUC for all the intra-abdominal tissues was increased significantly (20-427-fold). When i.p. IDLPLs were compared directly with i.v. IDLPLs, more modest changes were seen. There were increases in AUC for peritoneum (1.4-fold), ovary (1.3-fold), stomach (2.9-fold), pancreas (3.6-fold). small intestine (1.5-fold). colon (1.2-fold), gallbladder (5.1-fold) and adrenal gland (2.1-fold). These data support the development of i.p. liposomal chemotherapy for the treatment of intraperitoneal malignant disease.
比较了111In-DTPA标记的聚乙二醇化脂质体（IDLPL）和未包裹的111In-DTPA经腹腔（i.p.）和静脉（i.v.）途径给药在无肿瘤小鼠体内的生物分布和药代动力学。小鼠经腹腔或静脉注射0.37 MBq包裹在脂质体中的111In-DTPA或作为未包裹剂的111In-DTPA。在5分钟至192小时内解剖各种组织以确定生物分布和药代动力学。与未包裹的111In-DTPA相比，经腹腔途径注射IDLPL导致腹膜中浓度（AUC）-时间曲线下面积增加74倍。同样，所有腹腔内组织的AUC均显著增加（20 - 427倍）。当将腹腔IDLPL与静脉IDLPL直接比较时，观察到的变化较小。腹膜（1.4倍）、卵巢（1.3倍）、胃（2.9倍）、胰腺（3.6倍）、小肠（1.5倍）、结肠（1.2倍）、胆囊（5.1倍）和肾上腺（2.1倍）的AUC均增加。这些数据支持开发用于治疗腹腔恶性疾病的腹腔脂质体化疗。
