Small-scale preparation of perfluorocarbon-nanoemulsions utilizing dual centrifugation
Small-scale preparation of perfluorocarbon-nanoemulsions utilizing dual centrifugation
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DOI：
10.1016/j.ijpharm.2019.118753
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发表时间：
2019-12-15
影响因子：
5.8
通讯作者：
Massing, U.
中科院分区：
文献类型：
--
作者：
Kraemer, W.;Schubert, R.;Massing, U.
背景资料：由PFC和磷脂（PL）通过均质化制成的全氟碳纳米乳液（PFC-NE）对于单核细胞的体内-F-19标记以及随后在磁共振成像（MRI）中的发炎组织的体内-F-19标记是最佳的。在体内使用的PFC-NE的必要要求是无菌性，合适的液滴大小和没有免疫激活脂质体，这是一个典型的副产品的homogenizing process.Methods和结果：为了满足这些要求，我们开发了一种无菌瓶内制备技术PFC-NE的基础上双离心（DC）通过测试不同的PFC/磷脂比以及添加剂的应用。研究了两种不同的PFC，全氟辛基溴（PFOB）和全氟-15-冠-5-醚（PFCE）。通过动态光散射评估粒度，通过cryoTEM评估NE形态。当使用过量的PL（8.7%（m/m）的所利用的PFC，z-ave：180 nm，pdi：0.2）时，DC均化是最佳的。实施通过离心的纯化方法以去除在均质化期间由过量PL形成的脂质体。通过磷脂分析和PFC定量通过密度和声速measurements.Conclusion：DC结合短离心纯化的成功被证明是一种快速，可靠的方式，小规模的无菌PFCNE生产F-19 MRI被动靶向实验的单核细胞和炎症组织。
Background: Perfluorocarbon-nanoemulsions (PFC-NE) made of PFC and phospholipids (PL) by homogenization are optimal for in vivo-F-19 labelling of monocytes and subsequently of inflamed tissues in magnetic resonance imaging (MRI). Necessary requirements for in vivo use of PFC-NE are sterility, suitable droplet sizes and the absence of immune activating liposomes, which are a typical byproduct of the homogenization process.Methods and results: To meet these requirements, we developed an aseptic in-vial preparation technique for PFC-NE based on dual centrifugation (DC) by testing different PFC/phospholipid ratios as well as the application of additives. Two different PFC, perfluorooctylbromide (PFOB) and perfluoro-15-crown-5-ether (PFCE), were investigated. Particle sizes were assessed by dynamic light scattering and NE morphology by cryoTEM. DC homogenization was optimal when using an excess of PL (8.7 % (m/m) of utilized PFC, z-ave: 180 nm, pdi: 0.2). A purification approach by centrifugation was implemented to remove liposomes formed from the excess of PL during homogenization. The purification success was proven by phospholipid assay and PFC quantification via density and sound velocity measurements.Conclusion: DC in combination with a short centrifugation is a fast and reliable way of small-scale aseptic PFCNE production for F-19 MRI passive-targeting experiments of monocytes and inflamed tissues.