Merodio M, Irache J M, Eclancher F, Mirshahi M, Villarroya H
Centro Galénico. Universidad de Navarra. Ap. 177-31080 Pamplona. Spain.
J Drug Target. 2000;8(5):289-303. doi: 10.3109/10611860008997907.
Experimental allergic encephalomyelitis (EAE) is an autoimmune disease characterised by a disruption of the blood-brain barrier (BBB), demyelination and a relevant inflammatory reaction with an intense infiltration of macrophages. These neurological disorders are similar to those observed in the multiple sclerosis (MS) disease. The use of different liposomes and adeno-associated virus has been proposed for improving the treatment of this pathogenesis. The aim of this work was to evaluate the potential and capacity of albumin nanoparticles to reach the central nervous system (CNS) in EAE-induced rats. For this purpose, the distribution of biotinylated nanoparticles within the CNS was studied. Albumin carriers were mainly found in the lumbar portion of the spinal cord, overlying the meningeal and perivascular areas. The optic chiasma, iris and the area of the Purkinje cells of the cerebellum revealed also an intense presence of these carriers. Finally, immunohistochemical studies also revealed that circulating macrophages (ED1), which migrate to damaged sites, and resident activated microglial cells (OX42) were involved in the distribution of albumin nanoparticles. In summary, the use of nanoparticles may be useful for the design of new pharmaceutical dosage forms able to target the lesions associated with alterations of the BBB.
实验性自身免疫性脑脊髓炎(EAE)是一种自身免疫性疾病,其特征为血脑屏障(BBB)破坏、脱髓鞘以及伴有巨噬细胞强烈浸润的相关炎症反应。这些神经功能障碍与在多发性硬化症(MS)中观察到的相似。已提出使用不同的脂质体和腺相关病毒来改善这种发病机制的治疗。这项工作的目的是评估白蛋白纳米颗粒在EAE诱导的大鼠中到达中枢神经系统(CNS)的潜力和能力。为此,研究了生物素化纳米颗粒在中枢神经系统内的分布。白蛋白载体主要存在于脊髓的腰部,覆盖脑膜和血管周围区域。视交叉、虹膜和小脑浦肯野细胞区域也显示出这些载体的大量存在。最后,免疫组织化学研究还表明,迁移到受损部位的循环巨噬细胞(ED1)和常驻活化小胶质细胞(OX42)参与了白蛋白纳米颗粒的分布。总之,纳米颗粒的使用可能有助于设计能够靶向与血脑屏障改变相关病变的新型药物剂型。