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通过 PMNs 实现 LbL 涂层微载体的相互作用、摄取和处理。

Interaction, uptake, and processing of LbL-coated microcarriers by PMNs.

机构信息

Institute for Medical Physics and Biophysics, Medical Faculty, University of Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany.

出版信息

Cytometry A. 2011 Dec;79(12):979-89. doi: 10.1002/cyto.a.21145. Epub 2011 Oct 11.

Abstract

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 CaCO(3) microcarriers as AIS transporter system targeted at PMNs is investigated. The time-dependent interaction of protamine sulfate and dextran sulfate multilayer-coated 5 μm ± 1 μm CaCO(3) carriers with PMNs, in comparison with the usage of SiO(2) carriers as monodisperse model system of defined sizes (1, 3, and 5 μm), 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 CaCO(3) 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.

摘要

功能化的微载体或空心胶囊可输送活性药物,为细胞内药物输送提供了机会。这些药物输送系统的一个很有前途的应用是将固定化抗炎物质(AIS)直接输送和释放到多形核白细胞(PMN)中,PMN 在炎症过程中起着关键作用。将 AIS 递送到发炎组织中,可以减轻慢性炎症过程中发生的组织破坏,并促进这些过程的终止。在这项研究中,研究了靶向 PMN 的功能化 CaCO3 微载体作为 AIS 输送系统的能力。与使用 SiO2 载体作为具有定义尺寸的单分散模型系统(1、3 和 5 μm)相比,硫酸鱼精蛋白和硫酸葡聚糖多层包覆的 5 μm ± 1 μm CaCO3 载体与 PMN 的时间依赖性相互作用表明,在 2 至 24 小时的共孵育期间,载体/细胞相互作用和摄取足够充分。此外,通过 PMN 刺激使微载体暴露于模拟初级颗粒/吞噬体条件的环境中。用细胞上清液孵育 CaCO3 微载体 24 小时内会发生部分多层分解(三到五层),允许 AIS 在 PMN 寿命较短的时间内逐渐释放。这一观察结果表明,该药物输送系统在免疫活性细胞内具有潜在的应用前景,并可能为慢性疾病的治疗开辟新的替代方法。

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