Rate of biodistribution of STEALTH® liposomes to tumor and skin:: influence of liposome diameter and implications for toxicity and therapeutic activity
Rate of biodistribution of STEALTH® liposomes to tumor and skin:: influence of liposome diameter and implications for toxicity and therapeutic activity
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DOI：
10.1016/s0005-2736(02)00661-2
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发表时间：
2003-01-10
影响因子：
3.4
通讯作者：
Allen, TM
中科院分区：
文献类型：
--
作者：
Charrois, GJR;Allen, TM
研究了直径对STEALTH（R）脂质体进入小鼠肿瘤（4 T1鼠乳腺癌）和皮肤组织（皮肤和爪）的药代动力学和生物分布的影响，以确定脂质体积累的时间过程，并确定是否可以通过改变脂质体尺寸来实现脂质体优先积累到肿瘤中而不是皮肤或爪中。选择这些组织是因为Caelyx（TM）/Doxil（R）在人体中的剂量限制性毒性是掌跖红斑感觉迟钝，一种皮肤毒性。我们检查了四种直径的脂质体：82，101，154或241 nm。具有三种最小直径的脂质体显示出相似的蓄积特征，在所有三种目标组织中均显著高于最大脂质体。我们不能实现脂质体仅基于大小优先积聚到肿瘤中而不是皮肤或爪中，如肿瘤与皮肤和肿瘤与爪的比率所证明的。然而，这三种组织中脂质体蓄积的时间过程存在差异。脂质体水平在24小时内在肿瘤和爪中达到平台，而皮肤水平在24和48小时之间达到平台。在相同的模型中测试了三种直径（100、157和255 nm）的脂质体阿霉素的治疗活性。所有制剂均延迟肿瘤生长，100或157 nm的脂质体与255 nm的脂质体同样有效且上级。(C)2002 Elsevier Science B. V.保留所有权利。
The influence of diameter on the pharmacokinetic and biodistribution of STEALTH(R) liposomes into the tumor (4T1 murine mammary carcinoma) and cutaneous tissues (skin and paws) of mice was studied to ascertain the time course of liposome accumulation and to determine if a preferential accumulation of liposomes into tumor over skin or paws could be achieved by altering liposome size. These tissues were chosen as the dose-limiting toxicity for Caelyx(TM)/Doxil(R) in humans is palmar-plantar erythrodysesthesia, a cutaneous toxicity. We examined liposomes of four diameters: 82, 101, 154, or 241 nm. Liposomes with the three smallest diameters showed similar accumulation profiles that were significantly higher than the largest liposomes in all three tissues of interest. We were unable to achieve a preferential accumulation of liposomes into tumor over skin or paws based on size alone, as evidenced by the tumor to skin and tumor to paw ratios. However, there were differences in the time courses of liposome accumulation in these three tissues. Liposome levels plateaued in tumors and paws within 24 h, whereas skin levels plateaued between 24 and 48 h. The therapeutic activity of liposomal doxorubicin of three diameters (100, 157, and 255 nm) was tested in the same model. All formulations delayed tumor growth, with liposomes of 100 or 157 nm being equally efficacious and superior to liposomes of 255 nm. (C) 2002 Elsevier Science B.V. All rights reserved.