Tumor-specific antibody-mediated targeted delivery of Doxil® reduces the manifestation of auricular erythema side effect in mice
Tumor-specific antibody-mediated targeted delivery of Doxil® reduces the manifestation of auricular erythema side effect in mice
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DOI：
10.1016/j.ijpharm.2008.01.041
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发表时间：
2008-06-05
影响因子：
5.8
通讯作者：
Torchilin, Vladimir P.
中科院分区：
文献类型：
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作者：
Elbayoumi, Tamer A.;Torchilin, Vladimir P.
与Doxil（R）治疗相关的小鼠皮肤粘膜反应被鉴定为耳红斑（AE）。鉴于Doxil（R）对肿瘤的免疫靶向也被发现影响其全身生物分布模式，因此尝试开发Doxil（R）的特异性靶向以减少这种不良反应的表现。这个问题具有普遍意义，因为皮肤反应通常会导致患者Doxil（R）给药方案的改变，并可能随后损害癌症治疗的治疗结果。使用荷瘤小鼠研究了与抗癌单克隆抗体2C 5（mAb 2C 5）偶联的肿瘤靶向Doxil（R）（临床使用的抗癌制剂）的生物分布和皮肤组织蓄积效应以及由Doxil（R）应用引起的AE。与原始Doxil（R）相比，用mAb 2C 5修饰Doxil（R）导致多柔比星的正常皮肤积累的显著减少，并且AE显著减少。使用mAb 2C 5修饰的多柔比星负载的长循环脂质体，AE的频率降低了3 - 4倍。因此，用抗癌mAb 2C 5靶向Doxil（R）不仅可以增加药物的肿瘤特异性积累，而且还可以减少原始Doxil（R）治疗的皮肤副作用。(c)2008 Elsevier B. V.保留所有权利。
A mucocutaneous reaction in mice associated with Doxil (R) treatment was identified as auricular erythema (AE). Given that the immuno-targeting of Doxil (R) to tumors was found to influence also its systemic biodistribution pattern, the attempt was made to exploit a specific targeting of Doxil (R) to reduce the manifestation of this adverse reaction. This problem is of general significance, since cutaneous reactions often lead to alterations of Doxil (R) dosing regimen in patients and might subsequently compromise the therapeutic outcome of cancer treatment. Tumor-bearing mice were used to study the biodistribution and skin-tissue accumulation effects of the tumor-targeted Doxil (R) (the clinically used anti-cancer formulation) coupled with the anti-cancer monoclonal 2C5 antibody (mAb 2C5) as well as AE caused by Doxil (R) application. The modification of Doxil (R) with mAb 2C5 resulted in a significant decrease in the normal skin accumulation of doxorubicin compared to original Doxil (R) and substantially reduced AE. The frequency of AE was decreased by three to fourfold with the mAb 2C5-modified doxorubicin-loaded long-circulating liposomes. Thus, targeting of Doxil (R) with the anti-cancer mAb 2C5 not only can increase the tumor-specific accumulation of the drug, but also diminishes the cutaneous side effect of the original Doxil (R) therapy. (c) 2008 Elsevier B.V. All rights reserved.