We investigated the potential for systemic and local toxicity after administration of empty nanosized anionic and cationic PEGylated-micelles and non-PEGylated liposomes, without a ligand attached, intended for use in drug-delivery systems. The particles were administered to 5-6-week-old male rats by three intravenous (IV) administrations over a period of one week at a dose of 100 mg/kg bodyweight or after a single intracerebroventricular (ICV) injection at a dose of 50 µg. The particles were stable and well characterised with respect to size and zeta potential. ICV administration of cationic particles was associated with histological changes near the injection site (hippocampus). Here, we detected focal infiltration with phagocytic cells, loss of neurons and apoptotic cell death, which were not observed after administration of the vehicle. No significant difference was found after IV or ICV administration of the anionic micelles with regard to haematology, clinical chemistry parameters or at the pathological examinations, as compared to control animals. Our study suggests that ICV delivery of cationic particles to the brain tissue is associated with toxicity at the injection site.

中文翻译：

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对大鼠脑中带正电荷和带负电荷的纳米颗粒的差异毒理学响应。

我们研究了空的纳米和阴离子聚乙二醇化胶束和非聚乙二醇化脂质体（未连接配体）的全身和局部毒性的潜力，这些配体用于配药系统。在一周内，以100 mg / kg体重的剂量，或在以50的剂量单次脑室内（ICV）注射后，通过三次静脉内（IV）给药，将颗粒给药至5-6周龄的雄性大鼠微克。颗粒是稳定的并且就尺寸和ζ电位而言具有良好的特征。阳离子颗粒的ICV给药与注射部位（海马）附近的组织学变化有关。在这里，我们检测到吞噬细胞的局灶性浸润，神经元丢失和凋亡性细胞死亡，这在施用媒介物后未观察到。与对照动物相比，在静脉内或静脉内施用阴离子胶束后，在血液学，临床化学参数或病理学检查方面没有发现显着差异。我们的研究表明，阳离子颗粒向大脑组织的ICV释放与注射部位的毒性有关。