Antitumor activity and tumor localization of liposomal glucocorticoids in B16 melanoma-bearing mice
Antitumor activity and tumor localization of liposomal glucocorticoids in B16 melanoma-bearing mice
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DOI：
10.1016/j.jconrel.2008.01.008
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发表时间：
2008-04-21
影响因子：
10.8
通讯作者：
Schiffelers, Raymond M.
中科院分区：
文献类型：
--
作者：
Banciu, Manuela;Fens, Marcel H. A. M.;Schiffelers, Raymond M.
封装在长循环脂质体 (LCL) 中的泼尼松龙磷酸二钠 (PLP) (LCL-PLP) 在单剂量 20 mg/kg 后可抑制肿瘤生长 80-90%，而游离形式的 PLP 在相同的单剂量下完全无效。为了概括我们对 LCL-PLP 的研究结果，研究了除 PLP 之外含有合成糖皮质激素的 LCL (LCL-GC) 的抗肿瘤活性和副作用。除PLP外，根据激活人糖皮质激素受体的效力差异，选择布地奈德磷酸二钠、地塞米松磷酸二钠和甲泼尼龙磷酸二钠。本研究表明，每个GC的肿瘤定位受LCL的转运能力控制，LCL由二棕榈酰磷脂酰胆碱、胆固醇和聚乙二醇2000-二硬脂酰磷脂酰乙醇胺组成，摩尔比为1.85:1.0:0.15。 LCL-GC 的抗肿瘤效力很大程度上取决于所封装的 GC 类型的效力。 LCL 封装的布地奈德磷酸二钠 (LCL-BUP) 具有最高的抗肿瘤活性，这可能是由于 LCL 封装的 BUP 比其他三种 GC 类型的效力要高得多。 LCL-BUP 的高效力带来了发生强烈副作用的风险。然而，在3 mg/kg的剂量下，LCL-BUP是非常有效的，并且没有出现不良反应。 (c) 2008 Elsevier B.V. 保留所有权利。
Prednisolone disodium phosphate (PLP) encapsulated in long-circulating liposomes (LCL) (LCL-PLP) inhibited tumor growth by 80-90% after a single dose of 20 mg/kg, whereas PLP in the free form was completely ineffective at the same single dose. To generalize our findings with LCL-PLP, the antitumor activity and side effects of LCL containing synthetic glucocorticoids (LCL-GC) other than PLP were investigated. In addition to PLP, budesonide disodium phosphate, dexamethasone disodium phosphate, and methylprednisolone disodium phosphate were selected based on the difference in their potency to activate the human glucocorticoid receptor. The present study shows that the tumor localization of each GC is governed by the transport capacity of the LCL composed of dipalmitoylphosphatidylcholine, cholesterol, and polyethylene glycol 2000-distearoylphosphatidylethanolamine in a molar ratio of 1.85:1.0:0.15. The antitumor potency of the LCL-GC strongly depends on the potency of the type of GC encapsulated. LCL-encapsulated budesonide disodium phosphate (LCL-BUP) had the highest antitumor activity which is likely due to the much higher potency of BUP encapsulated in LCL versus the other three GC types. The high potency of LCL-BUP confers the risk for occurrence of strong side effects. However, at the dose of 3 mg/kg, LCL-BUP was highly efficacious without the occurrence of adverse effects. (c) 2008 Elsevier B.V. All rights reserved.