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首页> 外文期刊>Biomaterials Science >Induction of a higher-ordered architecture in glatiramer acetate improves its biological efficiency in an animal model of multiple sclerosis
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Induction of a higher-ordered architecture in glatiramer acetate improves its biological efficiency in an animal model of multiple sclerosis

机译：诱导Glatiramer醋酸盐中较高有序的结构提高了多发性硬化的动物模型中的生物学效率

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摘要

Glatiramer acetate (GA), a linear random copolypeptide, is a first-line treatment for multiple sclerosis (MS). A major concern, however, is that GA treatment is associated with adverse effects and poor patient adherence due to the need for frequent injections. Here we describe improved performance of the polymeric drug, even at low doses with less-frequent injections, through the modification of its architecture into a star-shaped GA (sGA). In a sGA, multiple GAs are covalently linked onto a core, which greatly changes their properties such as molecular weight, size, and shape. The spherical sGA is retained longer in the body after intraperitoneal injection, and is more readily internalized by RAW 264.7 macrophage cells and bone marrow-derived dendritic cells than GA. In C57BL/6 mice induced with experimental autoimmune encephalitis, a mouse model for MS, sGA treatment exerts disease amelioration effect that is significantly better than that of GA despite a lower dose and less frequent injection. Moreover, spinal cord pathologies of demyelination and leukocyte infiltration are dramatically less pronounced in the sGA treatment condition compared to the GA treatment condition. Thus, we propose that sGA with a higher-ordered architecture offers an attractive and potentially viable treatment option for MS patients.
机译：Glatiramer醋酸酯（Ga），一种线性随机共肽，是多发性硬化（MS）的一线处理。然而，主要关注的是，由于需要频繁注射，GA治疗与不良反应和患者依从性有关。在这里，我们描述了聚合物药物的改善性能，即使在低剂量的低剂量，通过将其建筑的改变为星形GA（SGA）。在SGA中，多种气体与芯中共价连接，这大大改变了它们的性质，例如分子量，尺寸和形状。在腹膜内注射后，球形SGA在体内保持较长，并且通过Raw 264.7巨噬细胞和骨髓衍生的树突细胞更容易内化。在用实验性自身免疫脑炎诱导的C57BL / 6小鼠中，SGA治疗的小鼠模型施加疾病改善效果，尽管注射较低，但注射频率较小，但仍然明显优于GA的疾病改善效果。此外，与GA处理条件相比，脱髓鞘和白细胞浸润的脊髓病理和白细胞浸润在SGA治疗条件下显着显着。因此，我们提出具有更高订单架构的SGA为MS患者提供有吸引力和潜在的可行的治疗选择。

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