Interaction, Uptake, and Processing of LbL-Coated Microcarriers by PMNs

Interaction, Uptake, and Processing of LbL-Coated Microcarriers by PMNs
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DOI:
10.1002/cyto.a.21145
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发表时间:
2011-12-01
期刊:
影响因子:
3.7
通讯作者:
Reibetanz, Uta
Reibetanz, Uta
中科院分区:
生物学4区
文献类型:
--
作者:
Rathmann, Sophie;Schoenberg, Maria;Reibetanz, Uta

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功能化的微载体或中空胶囊运输活性剂提供了在细胞内递送药物的机会。这些药物递送系统的一个有前景的应用是将固定化的促炎物质(AIS)直接运输以及释放到多形核白细胞(PMNs)中,其在炎症过程中起关键作用。将AIS预期递送到发炎组织中可以减轻慢性炎症期间发生的组织破坏,以及促进这些过程的终止。在这项研究中,功能化的碳酸钙微载体作为AIS转运系统针对中性粒细胞的能力进行了研究。硫酸鱼精蛋白和硫酸葡聚糖多层涂层5 μ m +/- 1 μ m CaCO 3载体与PMN的时间依赖性相互作用,与使用SiO2载体作为确定尺寸(1,3和5 μ m)的单分散模型系统相比,揭示了足够的载体/细胞相互作用和2至24小时之间的共孵育期的摄取。此外,在通过PMN刺激的吞噬作用后,将微载体暴露于模拟初级颗粒/吞噬体条件的环境。CaCO 3微载体与细胞上清液的孵育在24小时内表现出部分多层分解(三至五层),允许AIS在短的PMN寿命内逐渐释放。这一观察结果表明,这种药物递送系统在免疫活性细胞内的潜在应用,并可能为治疗慢性疾病的新替代方案开辟道路。(C)2011年国际细胞计数促进学会
Functionalized microcarriers or hollow capsules transporting active agents offer the opportunity for drug delivery inside cells. A promising application of these drug delivery systems is the direct transport as well as the release of immobilized antiinflammatory substances (AIS) into polymorphonuclear leukocytes (PMNs), which play a key role in the course of inflammatory processes. The intended delivery of AIS into the inflamed tissue could alleviate tissue destruction taking place during chronic inflammation, as well as facilitate the termination of these processes. In this study, the capability of functionalized CaCO3 microcarriers as AIS transporter system targeted at PMNs is investigated. The time-dependent interaction of protamine sulfate and dextran sulfate multilayer-coated 5 mu m +/- 1 mu m CaCO3 carriers with PMNs, in comparison with the usage of SiO2 carriers as monodisperse model system of defined sizes (1, 3, and 5 mu m), reveals a sufficient carrier/cell interaction and uptake for coincubation periods between 2 and 24 h. Furthermore, the microcarriers are exposed to an environment simulating primary granule/phagosomal conditions after phagocytosis by means of PMN stimulation. The incubation of CaCO3 microcarriers with cell supernatant demonstrates a partial multilayer decomposition (three to five layers) within 24 h, allowing the gradual release of AIS within the short PMN life span. This observation suggests a potential application for this drug delivery system inside immunologically active cells and may open the way to new alternatives in the treatment of chronic processes. (C) 2011 International Society for Advancement of Cytometry