Effects of PEGylation on the physicochemical properties and in vivo distribution of organic nanotubes.
Effects of PEGylation on the physicochemical properties and in vivo distribution of organic nanotubes.
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DOI：
10.2147/ijn.s75604
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发表时间：
2014
影响因子：
8
通讯作者：
Masuda M
中科院分区：
文献类型：
--
作者：
Ding W;Minamikawa H;Kameta N;Shimizu T;Masuda M
有机纳米管（ONTs）在药物纳米载体中的应用最终需要在活体动物中进行验证。为了提高ONT在生物介质中的分散性和体内分布，通过将ONT形成的脂质与5-20摩尔%的PEG-脂质类似物（PEG-脂质）共组装，将ONT的外表面与聚乙二醇（PEG）进行了功能化。首先，研究了聚乙二醇化对ONTs的形态和分散性等心理化学性质的影响。ONTs的聚乙二醇化略微减少了平均长度，并有效地阻止了其在磷酸盐缓冲盐水（PBS）中的聚集。聚乙二醇化的ONTs甚至在至少95°C的水分散中表现出很高的热稳定性。其次，差示扫描量热法和粉末x射线衍射表明，约10 mol%的peg -脂质完全融入到ONTs中，而20 mol%的peg -脂质在共组装过程中发生了部分相分离。在热差扫描量热法中，在冻干条件下，含5 mol% peg -脂的聚乙二醇化ONTs在180°C以上没有相分离的迹象，而含10 mol%和20 mol% peg -脂的聚乙二醇化ONTs在120°C以上有相分离的迹象。最后，PEGylation显著影响了小鼠的组织分布，延长了其在血液中的停留时间。非聚乙二醇化的ONTs在静脉输注后迅速从循环中清除，优先在肺中积累，而聚乙二醇化的ONTs主要滞留在肝脏中，可在血液中循环长达24小时。本研究为聚乙二醇化ONTs的物理化学性质和体内分布行为提供了有价值的信息，为其在药物纳米载体中的潜在应用提供了依据。
Application of organic nanotubes (ONTs) into drug nanocarriers ultimately requires validation in live animals. For improving the dispersibility in biological media and in vivo distribution, the outer surface of an ONT was functionalized with polyethylene glycol (PEG) via the coassembly of an ONT-forming lipid with 5–20 mol% of a PEG-tethered lipid analogue (PEG-lipid). Firstly, the effect of PEGylation on the psysicochemical properties of ONTs, such as morphology and dispersibility, was investigated. PEGylation of ONTs slightly reduced the average length and effectively prevented the aggregation in phosphate-buffered saline (PBS). The PEGylated ONTs even showed high thermal stability in aqueous dispersion at least up to 95°C. Secondly, differential scanning calorimetry and powder X-ray diffraction indicated that ~10 mol% of PEG-lipid was completely incorporated into the ONTs, while 20 mol% of PEG-lipid encountered a partial phase separation during coassembly. In the heating differential scanning calorimetry runs, the resultant PEGylated ONTs with 5 mol% PEG-lipid showed no sign of phase separation up to 180°C under lyophilized condition, while those with 10 mol% and 20 mol% PEG-lipid showed some phase separation of the PEG-lipid above 120°C. Finally, PEGylation significantly affected the tissue distribution and prolonged the persistence time in the blood in mice. Non-PEGylated ONTs was quickly cleared from the circulation after intravenous infusion and preferentially accumulated in the lung, while PEGylated ONTs was mainly trapped in the liver and could circulate in the blood up to 24 hours. This study provided valuable information of physicochemical properties and the in vivo distribution behavior of PEGylated ONTs for their potential application into drug nanocarriers.