血管壁剪切应力决定了血管生成脂质体的聚集区域。

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Drug Delivery and Translational Research Pub Date : 2024-12-01 Epub Date: 2024-07-23 DOI:10.1007/s13346-024-01671-1
M Juliana Gomez-Garcia, Mahmoud Abdelkarim, David T Cramb, Sarah J Childs, Kristina D Rinker, Hagar I Labouta
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引用次数: 0

摘要

用于给药的纳米颗粒通常需要静脉给药,使其暴露在血管内的流体力下,但人们对血流对纳米颗粒给药的影响仍然知之甚少。在这里,我们利用转基因斑马鱼胚胎研究了荧光标记的 PEG 化脂质体的积累与各种血流动力学因素(如流速、壁剪应力 (WSS) 和流动模式)在各种血管中的关系。我们根据共焦图像重建了血管结构的三维模型,并利用计算流体动力学计算了局部 WSS、流速并确定了流动模式。荧光标记脂质体的空间分布随后被绘制在同一三维空间中,并与局部血液动力学参数相关联。通过将计算流体动力学与活体实验相结合,我们发现脂质体在 WSS 值介于 0.1-0.8 Pa 之间的血管区域聚集,显示出时间平均壁剪应力与脂质体活体定位之间的反向线性相关(R2 > 0.85)。有趣的是,流动模式似乎并不影响脂质体的聚集。总之,我们的研究结果表明,隐形脂质体具有被动靶向低流量血管(包括毛细血管和类似肿瘤血管网络的复杂血管)的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Blood vessel wall shear stress determines regions of liposome accumulation in angiogenic vasculature.

Blood vessel wall shear stress determines regions of liposome accumulation in angiogenic vasculature.

Nanoparticles used for drug delivery often require intravenous administration exposing them to fluid forces within the vasculature, yet the impact of blood flow on nanoparticle delivery remains incompletely understood. Here, we utilized transgenic zebrafish embryos to investigate the relationship between the accumulation of fluorescently labeled PEGylated liposomes and various hemodynamic factors (such as flow velocity, wall shear stress (WSS), and flow pattern) across a wide range of angiogenic blood vessels. We reconstructed 3D models of vascular structures from confocal images and used computational fluid dynamics to calculate local WSS, velocities, and define flow patterns. The spatial distribution of fluorescently labeled liposomes was subsequently mapped within the same 3D space and correlated with local hemodynamic parameters. Through the integration of computational fluid dynamics and in vivo experimentation, we show that liposomes accumulated in vessel regions with WSS between 0.1-0.8 Pa, displaying an inverse linear correlation (R2 > 0.85) between time-averaged wall shear stress and liposome localization in vivo. Interestingly, flow pattern did not appear to impact liposome accumulation. Collectively, our findings suggest the potential of stealth liposomes for passive targeting of low-flow vasculature, including capillaries and intricate angiogenic vasculature resembling that of tumor vessel networks.

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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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