Liposome-encapsulated prednisolone phosphate inhibits growth of established tumors in mice
Liposome-encapsulated prednisolone phosphate inhibits growth of established tumors in mice
复制标题
DOI：
10.1593/neo.04340
复制
发表时间：
2005-02-01
期刊：
影响因子：
4.8
通讯作者：
Storm, G
中科院分区：
文献类型：
--
作者：
Schiffelers, RM;Metselaar, JM;Storm, G
糖皮质激素可以抑制实体瘤的生长，可能是由于对血管生成的抑制作用。仅使用基于长时间高频率给药的治疗方案观察到游离药物的抗肿瘤作用。由于长循环脂质体在恶性肿瘤部位积聚，我们研究了脂质体封装的磷酸泼尼松龙的肿瘤抑制潜力。脂质体磷酸泼尼松龙可以剂量依赖性地抑制肿瘤生长，单次或每周剂量20 mg/kg对皮下B16.F10黑色素瘤和C26结肠癌小鼠肿瘤模型的肿瘤生长抑制率为80%至90%。即使以 50 mg/kg 的剂量给药，游离形式的磷酸泼尼松龙在这种低频治疗方案中也完全无效。体外研究未显示泼尼松龙（磷酸盐）对肿瘤细胞或内皮细胞增殖的抑制作用。组织学评估显示，脂质体磷酸泼尼松龙治疗的肿瘤包含一个具有野餐/坏死细胞区域的中心，这在未治疗的肿瘤或用游离药物治疗的肿瘤中并不明显。总之，本研究表明，低剂量、低频率的糖皮质激素脂质体制剂具有有效的抗肿瘤作用，为脂质体糖皮质激素作为新型抗肿瘤药物提供了希望。
Glucocorticoids can inhibit solid tumor growth possibly due to an inhibitory effect on angiogenesis. The antitumor effects of the free drugs have only been observed using treatment schedules based on high and frequent dosing for prolonged periods of time. As long-circulating liposomes accumulate at sites of malignancy, we investigated the tumor-inhibiting potential of liposome-encapsulated prednisolone phosphate. Liposomal prednisolone phosphate could inhibit tumor growth dose-dependently, with 80% to 90% tumor growth inhibition of subcutaneous B16.F10 melanoma and C26 colon carcinoma murine tumor models at 20 mg/kg by single or weekly doses. Prednisolone phosphate in the free form was completely ineffective at this low-frequency treatment schedule, even when administered at a dose of 50 mg/kg. In vitro studies did not show an inhibitory effect of prednisolone (phosphate) on tumor cell, nor on endothelial cell proliferation. Histologic evaluation revealed that liposomal prednisolone phosphate-treated tumors contained a center with areas of picnotic/necrotic cells, which were not apparent in untreated tumors or tumors treated with the free drug. In conclusion, the present study shows potent antitumor effects of liposomal formulations of glucocorticoids in a low dose and low-frequency schedule, offering promise for liposomal glucocorticoids as novel antitumor agents.