Gabizon A, Goren D, Barenholz Y
Sharett Institute of Oncology, Hadassah University Hospital, Jerusalem, Israel.
Isr J Med Sci. 1988 Sep-Oct;24(9-10):512-7.
In this report we review our preclinical studies on the antitumor efficacy of L-DXR, using negatively charged sonicated vesicles. Animal studies indicate that various L-DXR formulations are more active than F-DXR on tumors infiltrating the liver and spleen, organs where liposomes are accumulated, and are equally effective on bone marrow-residing leukemic cells. In contrast, F-DXR was more effective than L-DXR when i.v.-administered, mg-equivalent doses were tested against ascitic and subcutaneously implanted tumors. Intraperitoneal administration of L-DXR was significantly more effective and approximately twofold less toxic than F-DXR in the treatment of an ascitic tumor. The antitumor effect correlated well with differences in drug levels in the relevant anatomic areas. These observations stress the site-specific activity of L-DXR and its dependence on biodistribution factor.
在本报告中，我们回顾了我们使用带负电荷的超声破碎囊泡对L-DXR抗肿瘤疗效的临床前研究。动物研究表明，各种L-DXR制剂在浸润肝脏和脾脏（脂质体聚集的器官）的肿瘤上比F-DXR更具活性，并且对骨髓中的白血病细胞同样有效。相比之下，当静脉注射时，以毫克当量剂量测试对腹水瘤和皮下植入瘤时，F-DXR比L-DXR更有效。在治疗腹水瘤时，腹腔注射L-DXR比F-DXR显著更有效且毒性降低约两倍。抗肿瘤作用与相关解剖区域药物水平的差异密切相关。这些观察结果强调了L-DXR的位点特异性活性及其对生物分布因子的依赖性。
