Nanomedicines have gained much attention for the delivery of small molecules or nucleic acids as treatment options for many diseases. However, the transfer from experimental systems to in vivo applications remains a challenge since it is difficult to assess their circulation behavior in the body at an early stage of drug discovery. Thus, innovative and improved concepts are urgently needed to overcome this issue and to close the gap between empiric nanoparticle design, in vitro assessment, and first in vivo experiments using rodent animal models.

This study was focused on the zebrafish as a vertebrate screening model to assess the circulation in blood and extravasation behavior of nanoparticulate drug delivery systems in vivo. To validate this novel approach, monodisperse preparations of fluorescently labeled liposomes with similar size and zeta potential were injected into transgenic zebrafish lines expressing green fluorescent protein in their vasculature. Phosphatidylcholine-based lipids differed by fatty acid chain length and saturation. Circulation behavior and vascular distribution pattern were evaluated qualitatively and semi-quantitatively using image analysis. Liposomes composed of lipids with lower transition temperature (< 28 °C) as well as PEGylated liposomes showed longer circulation times and extravasation. In contrast, liposomes composed of lipids with transition temperatures > 28 °C bound to venous parts of the vasculature. This circulation patterns in the zebrafish model did correlate with published and experimental pharmacokinetic data from mice and rats.

Our findings indicate that the zebrafish model is a useful vertebrate screening tool for nanoparticulate drug delivery systems to predict their in vivo circulation behavior with respect to systemic circulation time and exposure.

纳米药物作为小疾病的治疗选择，已引起人们对小分子或核酸的广泛关注。但是，从实验系统到体内应用的转移仍然是一个挑战，因为在药物发现的早期很难评估它们在体内的循环行为。因此，迫切需要创新和改进的概念来克服这个问题，并缩小经验性纳米颗粒设计，体外评估和使用啮齿动物模型进行的首次体内实验之间的差距。

这项研究集中在斑马鱼作为脊椎动物筛选模型，以评估血液中的循环和体内纳米微粒药物递送系统的外渗行为。为了验证这种新方法，将具有相似大小和Zeta电位的荧光标记脂质体的单分散制剂注射到在其脉管系统中表达绿色荧光蛋白的转基因斑马鱼品系中。基于磷脂酰胆碱的脂质的脂肪酸链长度和饱和度不同。使用图像分析定性和半定量评估循环行为和血管分布模式。由具有较低转变温度（<28°C）的脂质组成的脂质体以及聚乙二醇化脂质体表现出更长的循环时间和外渗。相比之下，由过渡温度> 28°C的脂质组成的脂质体，结合到脉管系统的静脉部分。斑马鱼模型中的这种循环模式确实与来自小鼠和大鼠的已发表和实验的药代动力学数据相关。

我们的发现表明，斑马鱼模型是用于纳米颗粒药物传递系统的有用的脊椎动物筛选工具，可预测它们在体内的循环行为与全身循环时间和暴露量有关。