Effects of cellulose derivatives and poly(ethylene oxide)-poly(propylene oxide) tri-block copolymers (Pluronic® surfactants) on the properties of alginate based microspheres and their interactions with phagocytic cells
Effects of cellulose derivatives and poly(ethylene oxide)-poly(propylene oxide) tri-block copolymers (Pluronic® surfactants) on the properties of alginate based microspheres and their interactions with phagocytic cells
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DOI：
10.1016/s0168-3659(02)00281-x
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发表时间：
2002-12-13
影响因子：
10.8
通讯作者：
Bowersock, TL
中科院分区：
文献类型：
--
作者：
Kidane, A;Guimond, P;Bowersock, TL
本研究的目的是检测具有不同表面性质的海藻酸盐基微球的吞噬作用。与巨噬细胞的良好相互作用对于口服疫苗递送所用微球的摄取及后续处理至关重要。我们研究了海藻酸盐微球的大小和疏水性对细胞摄取的影响。我们还研究了制剂成分对吞噬细胞的毒性。海藻酸盐微球通过乳液 - 交联技术制备。对五种不同配方的微球在大小、疏水性、细胞摄取以及对巨噬细胞的毒性方面进行了评估。所检测的配方分别为：单独的海藻酸盐（A）、含甲基纤维素的海藻酸盐（AA）、含普朗尼克（Pluronic®）L61的AA（AA61）、含羟丙基甲基纤维素的海藻酸盐（AK3）以及含普朗尼克L61的AK3（AK3 61）。对有和没有聚 - L - 赖氨酸（PLL）涂层的微球都进行了测试。A、AA、AA61、AK3、AK3 61微球（MS）的平均体积大小分别为11、10.5、3.8、8.7和3.9微米。用PLL涂层后，平均体积大小分别为10.4、10、3.7、8.8和3.5微米。通过测量涂覆在载玻片上的微球的接触角来评估微球的疏水性。用测角仪测量的A、AA、AA61、AK3、AK3 61微球的接触角分别为20°、34.8°、71°、29°和80°，而涂覆PLL的那些微球的接触角分别为49.7°、55.8°、91°、48.25°和84.4°。利用流式细胞术进行的细胞摄取研究表明，涂覆PLL的AA61微球最常被小鼠巨噬细胞吞噬。在没有PLL涂层的那些微球之间，细胞摄取没有统计学上的显著差异。对巨噬细胞的毒性显示取决于微球与细胞的比例。这些研究表明，制剂能够以影响其作为疫苗递送系统给药时与体内细胞相互作用方式的途径，极大地影响海藻酸盐微球的物理特性。（C）2002爱思唯尔科学出版社（Elsevier Science B.V.）。保留所有权利。
The goal of this study was to examine the phagocytosis of alginate based microspheres with different surface properties. Favorable interaction with macrophages is critical for uptake subsequent processing of the microspheres used for oral vaccine delivery. We examined the effects of size of alginate microspheres and hydrophobicity on cellular uptake. We also examined the toxicity of formulation components to phagocytic cells. Alginate microspheres were made by the emulsion-cross-linking technique. Five different formulations of microspheres were evaluated for size, hydrophobicity, cellular uptake and toxicity to macrophages. The formulations examined were: alginate alone (A), alginate with methylcellulose (AA) AA with Pluronic(R) L61 (AA61), alginate with hydroxypropyl methylcellulose (AK3), and AK3 with Pluronico L61 (AK3 61). Microspheres with without poly-L-lysine (PLL) coating were tested. The mean volume sizes of A, AA, AA61, AK3, AK3 61 microspheres (MS) were 11, 10.5, 3.8, 8.7 and 3.9 mum, respectively. After coating them with PLL the mean volume sizes were 10.4, 10, 3.7, 8.8 and 3.5 pm, respectively. Hydrophobicity of the microspheres was evaluated by measuring contact angle on a glass slide coated with the microspheres. The contact angles measured using a goniometer on A, AA, AA61, AK3, AK3 61 MS were 20, 34.8, 71, 29 and 80degrees, respectively whereas those MS coated with PLL were 49.7, 55.8, 91, 48.25 and 84.4degrees, respectively. Cellular uptake studies using flow cytometery revealed that AA61 MS coated with PLL were phagocytosed most often by mouse macrophages. There was no statistically significant difference in cellular uptake among those MS without PLL coating. Toxicity to macrophages was shown to depend on the ratio of microspheres to cells. These studies suggest that formulation can dramatically affect the physical characteristics of alginate MS in ways that can affect how they will interact with cells in the body when administered as a vaccine delivery system. (C) 2002 Elsevier Science B.V. All rights reserved.