Development of Nanosome-Encapsulated Honokiol for Intravenous Therapy Against Experimental Autoimmune Encephalomyelitis
Development of Nanosome-Encapsulated Honokiol for Intravenous Therapy Against Experimental Autoimmune Encephalomyelitis
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DOI：
10.2147/ijn.s214349
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发表时间：
2020-01-01
影响因子：
8
通讯作者：
Jan, Tong-Rong
中科院分区：
文献类型：
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作者：
Hsiao, Yai-Ping;Chen, Hui-Ting;Jan, Tong-Rong
背景：厚朴具有抗炎和神经保护作用。然而，和诺明的水溶性差限制了其临床应用全身administration.Purpose：本研究旨在开发一种新的纳米囊封和诺明（NHNK）的静脉注射治疗小鼠实验性自身免疫性脑脊髓炎（EAE），模仿人类多发性sclerosis. Methods：纳米囊和NHNK通过使用超高压匀浆（UHPH）方法制备。在EAE症状的高峰期用NHNK或空纳米体治疗小鼠。结果：在纳米体制剂中含有和厚朴酚的NHNK储备液显示出单磷脂双层膜的结构，其良好地配制成粒径为48.0 +/-0.1nm，包封率为58.1 +/-4.2%。静脉注射NHNK可减轻EAE的严重程度，并显着减少脊髓脱髓鞘和炎症。结论：UHPH法制备的NHNK颗粒粒径均匀，包封率高，易于制备。静脉注射NHNK可通过抑制活化的小胶质细胞和Th1细胞向脊髓的浸润来减轻EAE的严重程度。总的来说，这些结果表明，NHNK制剂是一种治疗炎症性CNS疾病（如多发性硬化症）的前瞻性治疗方法。
Background: Honokiol has been reported to possess anti-inflammatory and neuroprotective activities. However, the poor aqueous solubility of honokiol limits its clinical application for systemic administration.Purpose: This study aims to develop a novel formulation of nanosome-encapsulated honokiol (NHNK) for intravenous therapy against mouse experimental autoimmune encephalomyelitis (EAE) that mimics human multiple sclerosis.Methods: Nanosomes and NHNK were prepared by using an ultra-high pressure homogenization (UHPH) method. Mice were treated with NHNK or empty nanosomes during the peak phase of EAE symptoms. Symptoms of EAE were monitored and samples of the spinal cord were obtained for histopathological examinations.Results: The stock of NHNK containing honokiol in the nanosome formulation, which showed the structure of single phospholipid bilayer membranes, was well formulated with the particle size of 48.0 +/- 0.1 nm and the encapsulation efficiency 58.1 +/- 4.2%. Intravenous administration of NHNK ameliorated the severity of EAE accompanied by a significant reduction of demyelination and inflammation in the spinal cord. Furthermore, NHNK decreased the number of IL-6(+), Iba-1(+) TNF+, Iba- 1(+) IL-12 p40(+), and CD3(+) IFN-gamma(+) cells infiltrating the spinal cord.Conclusion: The UHPH method simplified the preparation of NHNK with uniformly distributed nanosize and high encapsulation efficiency. Intravenous administration of NHNK ameliorated the severity of EAE by suppressing the infiltration of activated microglia and Th1 cells into the spinal cord. Collectively, these results suggest that the formulation of NHNK is a prospective therapeutic approach for inflammatory CNS diseases, such as multiple sclerosis.