Role of particle size in phagocytosis of polymeric microspheres
Role of particle size in phagocytosis of polymeric microspheres
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DOI：
10.1007/s11095-008-9562-y
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发表时间：
2008-08-01
影响因子：
3.7
通讯作者：
Mitragotri, Samir
中科院分区：
文献类型：
--
作者：
Champion, Julie A.;Walker, Amanda;Mitragotri, Samir
目的.聚合物微球被广泛研究用于药物和疫苗递送。然而，在施用到体内后，微球主要通过巨噬细胞的吞噬作用清除。虽然许多研究报道了吞噬作用的生化途径，但对吞噬作用对颗粒大小的依赖性知之甚少。在这里，我们调查了以前无法解释的依赖于颗粒大小的吞噬作用。大鼠肺泡巨噬细胞和IgG调理和非调理聚苯乙烯微球被用作模型巨噬细胞和药物递送颗粒。通过流式细胞术和延时视频显微镜检测细胞的吞噬、粘附和内化。直径为2-3 μ m的颗粒表现出最大的吞噬作用和附着。然而，内化速率不受颗粒尺寸的显着影响。假设2-3 μ m微球的最大附着源自巨噬细胞中膜皱褶的特征。通过渗透膨胀消除皱褶几乎消除了吞噬作用的特殊尺寸依赖性。提出了一个简单的数学模型来描述吞噬作用对颗粒大小的依赖性。吞噬作用对颗粒尺寸的依赖性主要源于附着步骤。这些结果揭示了控制药物递送颗粒尺寸分布和选择适合于避免或促进吞噬作用的尺寸的重要性。
Purpose. Polymeric microspheres are extensively researched for applications in drug and vaccine delivery. However, upon administration into the body, microspheres are primarily cleared via phagocytosis by macrophages. Although numerous studies have reported on the biochemical pathways of phagocytosis, relatively little is known about the dependence of phagocytosis on particle size. Here, we investigate the previously unexplained dependence of phagocytosis on particle size.Methods. Rat alveolar macrophages and IgG-opsonized and non-opsonized polystyrene microspheres were used as model macrophages and drug delivery particles. Phagocytosis, attachment and internalization were measured by flow cytometry and time-lapse video microscopy.Results. Particles possessing diameters of 2-3 mu m exhibited maximal phagocytosis and attachment. Rate of internalization, however, was not affected significantly by particle size. Maximal attachment of 2-3 mu m microspheres is hypothesized to originate from the characteristic features of membrane ruffles in macrophages. Elimination of ruffles via osmotic swelling nearly eliminated the peculiar size-dependence of phagocytosis. A simple mathematical model is presented to describe the dependence of phagocytosis on particle size.Conclusions. The dependence of phagocytosis on particle size originated primarily from the attachment step. These results reveal the importance of controlling drug delivery particle size distribution and selecting the size appropriate for avoiding or encouraging phagocytosis.