Hong Kelvin, Khwaja Afsheen, Liapi Eleni, Torbenson Michael S, Georgiades Cristos S, Geschwind Jean-Francois H
Division of Vascular and Interventional Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Clin Cancer Res. 2006 Apr 15;12(8):2563-7. doi: 10.1158/1078-0432.CCR-05-2225.
In the fight against cancer, new drug delivery systems are attractive to improve drug targeting of tumors, maximize drug potency, and minimize systemic toxicity. We studied a new drug delivery system comprising microspheres, with unique properties allowing delivery of large amounts of drugs to tumors for a prolonged time, thereby decreasing plasma levels. Liver tumors, unlike nontumorous liver, draw most of their blood supply from the hepatic artery. Exploiting this property, we delivered drug-eluting microspheres/beads (DEB) loaded with doxorubicin, intra-arterially, in an animal model of liver cancer (Vx-2).
The purpose of our study was to determine the pharmacokinetics and tumor-killing efficacy of DEB.
Our results show that plasma concentration of doxorubicin was minimal in the animals treated with DEB at all time points (0.009-0.05 micromol/L), suggesting high tumor retention of doxorubicin. This was significantly lower (70-85% decrease in plasma concentration) than control animals treated with doxorubicin intra-arterially. Within the tumor, doxorubicin concentration peaked at 3 days (413.5 nmol/g), remaining high to 7 days (116.7 nmol/g) before declining at 14 days (41.76 nmol/g), indicating continuous doxorubicin elution from beads. In control animals, peak tumor concentration of doxorubicin was 0.09 nmol/g. Tumor necrosis (approaching 100%) was greatest at 7 days, with minimal adverse local side effects reflected in liver function tests results. The plasma concentration of doxorubicinol (doxorubicin main metabolite) was minimal.
Our results support the concept of DEBs as an effective way to deliver drugs to tumor. This new technology may prove to be a useful weapon against liver cancer.
在抗癌斗争中，新型药物递送系统对于改善肿瘤药物靶向性、最大化药物效力以及最小化全身毒性具有吸引力。我们研究了一种由微球组成的新型药物递送系统，其独特性质能够使大量药物长时间递送至肿瘤，从而降低血浆水平。与非肿瘤性肝脏不同，肝肿瘤的大部分血液供应来自肝动脉。利用这一特性，我们在肝癌动物模型（VX-2）中经动脉递送了载有多柔比星的药物洗脱微球/微珠（DEB）。
我们研究的目的是确定DEB的药代动力学和肿瘤杀伤效果。
我们的结果表明，在所有时间点，接受DEB治疗的动物体内多柔比星的血浆浓度极低（0.009 - 0.05微摩尔/升），这表明多柔比星在肿瘤中的保留率很高。这显著低于经动脉接受多柔比星治疗的对照动物（血浆浓度降低70 - 85%）。在肿瘤内，多柔比星浓度在第3天达到峰值（413.�纳摩尔/克），在第7天仍保持较高水平（116.7纳摩尔/克），然后在第14天下降（41.76纳摩尔/克），这表明多柔比星持续从微珠中洗脱。在对照动物中，多柔比星的肿瘤峰值浓度为0.09纳摩尔/克。肿瘤坏死率（接近100%）在第7天最高，肝功能测试结果显示局部不良反应最小。多柔比星醇（多柔比星的主要代谢产物）的血浆浓度极低。
我们的结果支持DEB作为一种向肿瘤递送药物的有效方式的概念。这项新技术可能被证明是对抗肝癌的有用武器。
