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首页> 外文期刊>Colloids and Surfaces, B. Biointerfaces >Microspheres prepared with different co-polymers of poly(lactic-glycolic acid) (PLGA) or with chitosan cause distinct effects on macrophages
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Microspheres prepared with different co-polymers of poly(lactic-glycolic acid) (PLGA) or with chitosan cause distinct effects on macrophages

机译:用聚乳酸乙醇酸(PLGA)的不同共聚物或壳聚糖制备的微球对巨噬细胞有明显的影响

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摘要

Microencapsulation of bioactive molecules for modulating the immune response during infectious or inflammatory events is a promising approach, since microspheres (MS) protect these labile biomolecules against fast degradation, prolong the delivery over longer periods of time and, in many situations, target their delivery to site of action, avoiding toxic side effects. Little is known, however, about the influence of different polymers used to prepare MS on macrophages. This paper aims to address this issue by evaluating in vitro cytotoxicity, phagocytosis profile and cytokines release from alveolar macrophages (J-774.1) treated with MS prepared with chitosan, and four different co-polymers of PLGA [poly (lactic-co-glycolic acid)]. The five MS prepared presented similar diameter and zeta potential each other. Chitosan-MS showed to be cytotoxic to J-774.1 cells, in contrast to PLGA-MS, which were all innocuous to this cell linage. PLGA 5000-MS was more efficiently phagocytized by macrophages compared to the other MS tested. PLGA 5000-MS and 5002-MS induced significant production of TNF-alpha, while 5000-MS, 5004-MS and 7502-MS decreased spontaneous IL-6 release. Nevertheless, only ALGA 5002-MS induced significant NFkB/SEAP activation. These findings together show that MS prepared with distinct PLGA co-polymers are differently recognized by macrophages, depending on proportion of lactic and glycolic acid in polymeric chain, and on molecular weight of the co-polymer used. Selection of the most adequate polymer to prepare a microparticulate drug delivery system to modulate immunologic system may take into account, therefore, which kind of immunomodulatory response is more adequate for the required treatment. (C) 2015 Elsevier B.V. All rights reserved.
机译:微囊生物活性分子用于在传染性或炎性事件期间调节免疫反应是一种有前途的方法,因为微球(MS)保护这些不稳定的生物分子免于快速降解,延长较长时间的传递,在许多情况下,将其传递至作用部位,避免毒副作用。然而,关于用于制备MS的不同聚合物对巨噬细胞的影响知之甚少。本文旨在通过评估用壳聚糖制备的MS和PLGA的四种不同共聚物[聚(乳酸-共-乙醇酸)]处理的肺泡巨噬细胞(J-774.1)的体外细胞毒性,吞噬作用特征和细胞因子释放来解决这个问题。 )]。制备的五个质谱图呈现出相似的直径和zeta电位。与PLGA-MS相比,壳聚糖-MS对J-774.1细胞具有细胞毒性,而PLGA-MS均对该细胞谱系无害。与其他测试的MS相比,PLGA 5000-MS被巨噬细胞吞噬的效率更高。 PLGA 5000-MS和5002-MS诱导了TNF-alpha的大量产生,而5000-MS,5004-MS和7502-MS降低了自发IL-6的释放。但是,只有ALGA 5002-MS可以诱导显着的NFkB / SEAP激活。这些发现共同表明,由巨噬细胞不同地识别由不同的PLGA共聚物制备的MS,这取决于聚合物链中乳酸和乙醇酸的比例以及所用共聚物的分子量。因此,可以考虑选择最合适的聚合物以制备微粒药物递送系统以调节免疫系统,因此,哪种免疫调节反应更适合所需的治疗。 (C)2015 Elsevier B.V.保留所有权利。

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