A therapeutic strategy that can combat the multifaceted nature of neuroinflammation pathology was investigated. Thus, we fabricated PEG-PdLLA polymersomes and evaluated the efficacy in co-delivery of simvastatin (Sim, as a repurposed anti-inflammatory agent) with brain derived neurotrophic factor (BDNF, as an exogeneous trophic factor supplementation). Using LPS model of neuroinflammation, intranasal administration of combination drug-loaded polymersomes (containing both Sim and BDNF; Sim-BDNF-Ps) markedly down-regulated brain levels of cytokines compared to free drug and single-drug-loaded polymersomes. Further, Sim-BDNF-Ps effectively replenished brain level of BDNF that was depleted following neuroinflammation, resulting in a 2-fold BDNF increase versus untreated LPS control group. We found out that the efficiency of the combination drug-loaded polymersomes to suppress microglia activation in brain regions followed the order: frontal cortex > striatum > hippocampus. Our findings indicated that Sim-BDNF-Ps could effectively inhibit microglial-mediated inflammation as well as potentially resolve the neurotoxic microenvironment that is often associated with neuroinflammation.

研究了一种可以对抗神经炎症病理学多面性的治疗策略。因此，我们制造了PEG-PdLLA聚合物囊泡，并评估了辛伐他汀（Sim，作为一种改用的抗炎药）与脑源性神经营养因子（BDNF，作为一种外源性营养因子的补充剂）共同给药的效果。使用神经炎症的LPS模型，与游离药物和单一药物的聚合物囊泡相比，鼻内给药组合药物的聚合物囊泡（含Sim和BDNF； Sim-BDNF-Ps）显着下调了脑因子的细胞因子。此外，Sim-BDNF-Ps可有效补充神经发炎后消耗的BDNF脑水平，与未治疗的LPS对照组相比，BDNF升高2倍。我们发现结合药物的聚合物囊泡抑制大脑区域小胶质细胞活化的效率遵循以下顺序：额叶皮层>纹状体>海马体。我们的发现表明，Sim-BDNF-Ps可以有效抑制小胶质细胞介导的炎症，并可能解决通常与神经炎症相关的神经毒性微环境。