The increasing use in the last decade of PEGylated nanodrugs such as Doxil® has seen a rise in the number of associated occurrences of hypersensitivity reactions (HSRs). These reactions (also called infusion reactions or IR), can range from harmless symptoms to life-threatening reactions. Current means to prevent IR include the prophylactic use of antihistamines and steroids, but they cannot ensure total prevention. We previously showed that an intravenous injection of doxorubicin-free Doxil-like PEGylated nano-liposomes (Doxebo) prior to Doxil treatment suppresses Doxil-induced complement activation-related pseudoallergy (CARPA) in pigs, a model of human hypersensitivity reactions to Doxil. However, in order to use Doxebo to prevent Doxil-induced IR, we have to prove its safety and that it does not affect Doxil's performance. Here we show that Doxebo itself does not have toxic effects on the host or tumor, and it does not interfere with Doxil's antitumor activity in mice. Blood, microscopic and macroscopic organ evaluation of rats after repeated administration confirm the lack of intrinsic adverse effect of Doxebo. Likewise, the repeated injection of Doxebo before Doxil did not impact Doxil's pharmacokinetics in plasma and therefore does not cause accelerated blood clearance (ABC). Taken together with our previous publications, these data suggest that the injection of Doxebo prior to Doxil administration can help protect against Doxil-induced IR without adversely affecting treatment efficacy and safety.

中文翻译：

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Doxebo（不含阿霉素的无Doxil脂质体）可安全地用作预防对PEG化纳米药物的输注反应的预处理。

在最近十年中，诸如Doxil®之类的PEG化纳米药物的使用不断增加，已经出现了与超敏反应（HSR）相关的事件。这些反应（也称为输注反应或IR）的范围从无害症状到危及生命的反应。当前预防IR的手段包括预防性使用抗组胺药和类固醇，但它们不能确保全面预防。我们先前显示，在Doxil治疗之前静脉注射无阿霉素的Doxil样聚乙二醇化纳米脂质体（Doxebo）可以抑制猪中Doxil诱导的补体激活相关的假性变态反应（CARPA），这是人对Doxil的超敏反应模型。但是，为了使用Doxebo预防Doxil引起的IR，我们必须证明其安全性，并且不影响Doxil的性能。在这里，我们表明Doxebo本身对宿主或肿瘤没有毒性作用，并且不干扰Doxil在小鼠中的抗肿瘤活性。重复给药后对大鼠的血液，微观和宏观器官进行评估，证实了Doxebo缺乏内在的不良反应。同样，在Doxil之前重复注射Doxebo不会影响Doxil在血浆中的药代动力学，因此不会导致血液清除加快（ABC）。结合我们以前的出版物，这些数据表明，在服用多西尔之前注射多西博可以帮助预防多西尔引起的IR，而不会不利地影响治疗效果和安全性。重复给药后对大鼠的微观和宏观器官评估证实了Doxebo缺乏内在的不良反应。同样，在Doxil之前重复注射Doxebo不会影响Doxil在血浆中的药代动力学，因此不会导致血液清除加快（ABC）。结合我们以前的出版物，这些数据表明，在服用多西尔之前注射多西博可帮助预防多西尔引起的IR，而不会不利地影响治疗效果和安全性。重复给药后对大鼠的微观和宏观器官评估证实了Doxebo缺乏内在的不良反应。同样，在Doxil之前重复注射Doxebo不会影响Doxil在血浆中的药代动力学，因此不会导致血液清除加快（ABC）。结合我们以前的出版物，这些数据表明，在服用多西尔之前注射多西博可以帮助预防多西尔引起的IR，而不会不利地影响治疗效果和安全性。