Delivery of rapamycin to dendritic cells using degradable microparticles.
Delivery of rapamycin to dendritic cells using degradable microparticles.
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DOI：
10.1016/j.jconrel.2008.10.011
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发表时间：
2009-02-10
期刊：
影响因子：
--
通讯作者：
Little SR
中科院分区：
文献类型：
--
作者：
Jhunjhunwala S;Raimondi G;Thomson AW;Little SR
可降解微粒具有长期保护和释放药物的潜力，如果尺寸合适，可以被动地靶向体内的吞噬细胞。树突状细胞（DC）是一类已知在移植排斥中发挥重要作用的吞噬细胞。此前，我们已经证明用免疫抑制药物雷帕霉素治疗的DC具有抑制移植排斥的能力。在此，我们描述了一种将雷帕霉素细胞内储库递送至 DC 的策略。为了实现这一目标，将雷帕霉素封装到约 3.4 μm 大小的聚乳酸-乙醇酸 (PLGA) 微粒 (rapaMPs) 中，并在吞噬体内 (pH = 5) 和细胞外 (pH = 7.4) 条件下检查释放行为。据观察，与用可溶性雷帕霉素处理的 DC 相比，吞噬 rapaMP 4 天后，DC 激活 T 细胞的能力显着降低。因此，我们得出结论，与用细胞外雷帕霉素治疗 DC 相比，DC 特异性细胞内递送雷帕霉素在调节 DC 功能的能力方面具有更好的药物功效。
Degradable microparticles have the potential to protect and release drugs over extended periods and, if sized appropriately, can be passively targeted to phagocytic cells in vivo. Dendritic cells (DC) are a class of phagocytic cells known to play important roles in transplant rejection. Previously, we have demonstrated that DC treated with an immunosuppressive drug, rapamycin, have the ability to suppress transplant rejection. Herein, we describe a strategy to deliver an intracellular depot of rapamycin to DC. To achieve this, rapamycin was encapsulated into ∼3.4 μm sized poly(lactic-co-glycolic)acid (PLGA) microparticles (rapaMPs), and release behavior was examined under intra-phagosomal (pH = 5) and extracellular (pH = 7.4) conditions. It was observed that 4 days following phagocytosis of rapaMP, DC have significantly reduced ability to activate T cells, in comparison to DC treated with soluble rapamycin. Hence, we conclude that DC-specific intracellular delivery of rapamycin results in better efficacy of the drug, with respect to its ability to modulate DC function, when compared to treating DC with extracellular rapamycin.
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