Suppr超能文献

白蛋白衍生的全氟化碳基人工氧载体:物理化学特性及首次体内生物相容性评估

Albumin-derived perfluorocarbon-based artificial oxygen carriers: A physico-chemical characterization and first in vivo evaluation of biocompatibility.

作者信息

Wrobeln Anna, Laudien Julia, Groß-Heitfeld Christoph, Linders Jürgen, Mayer Christian, Wilde Benjamin, Knoll Tanja, Naglav Dominik, Kirsch Michael, Ferenz Katja B

机构信息

University of Duisburg-Essen, Institute for Physiological Chemistry, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany.

University of Duisburg-Essen, Institute for Physical Chemistry, CeNIDE, Universitaetsstr. 5, 45141 Essen, Germany.

出版信息

Eur J Pharm Biopharm. 2017 Jun;115:52-64. doi: 10.1016/j.ejpb.2017.02.015. Epub 2017 Feb 20.

Abstract

Until today, artificial oxygen carriers have not been reached satisfactory quality for routine clinical treatments. To bridge this gap, we designed albumin-derived perfluorocarbon-based nanoparticles as novel artificial oxygen carriers and evaluated their physico-chemical and pharmacological performance. Our albumin-derived perfluorocarbon-based nanoparticles (capsules), composed of an albumin shell and a perfluorodecalin core, were synthesized using ultrasonics. Their subsequent analysis by physico-chemical methods such as scanning electron-, laser scanning- and dark field microscopy as well as dynamic light scattering revealed spherically-shaped, nano-sized particles, that were colloidally stable when dispersed in 5% human serum albumin solution. Furthermore, they provided a remarkable maximum oxygen capacity, determined with a respirometer, reflecting a higher oxygen transport capacity than the competitor Perftoran®. Intravenous administration to healthy rats was well tolerated. Undesirable effects on either mean arterial blood pressure, hepatic microcirculation (determined by in vivo microscopy) or any deposit of capsules in organs, except the spleen, were not observed. Some minor, dose-dependent effects on tissue damage (release of cellular enzymes, alterations of spleen's micro-architecture) were detected. As our promising albumin-derived perfluorocarbon-based nanoparticles fulfilled decisive physico-chemical demands of an artificial oxygen carrier while lacking severe side-effects after in vivo administration they should be advanced to functionally focused in vivo testing conditions.

摘要

直到如今,人工氧载体的质量仍未达到可用于常规临床治疗的令人满意的程度。为了填补这一空白,我们设计了基于白蛋白的全氟碳纳米颗粒作为新型人工氧载体,并评估了它们的物理化学和药理性能。我们基于白蛋白的全氟碳纳米颗粒(胶囊)由白蛋白外壳和全氟萘烷内核组成,通过超声合成。随后通过扫描电子显微镜、激光扫描显微镜和暗场显微镜以及动态光散射等物理化学方法对其进行分析,结果显示这些颗粒呈球形,尺寸为纳米级,当分散在5%的人血清白蛋白溶液中时具有胶体稳定性。此外,用呼吸计测定发现它们具有显著的最大氧容量,这表明其氧运输能力高于竞争对手Perftoran®。对健康大鼠进行静脉注射后,大鼠耐受性良好。未观察到对平均动脉血压、肝微循环(通过体内显微镜检查测定)有不良影响,也未观察到胶囊在除脾脏外的其他器官中有任何沉积。检测到了一些对组织损伤的轻微的剂量依赖性影响(细胞酶释放、脾脏微结构改变)。由于我们有前景的基于白蛋白的全氟碳纳米颗粒满足了人工氧载体的决定性物理化学要求,且在体内给药后没有严重的副作用,因此应推进到功能聚焦的体内测试条件下。

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验