Development of Nanosome-Encapsulated Honokiol for Intravenous Therapy Against Experimental Autoimmune Encephalomyelitis

• Published in: International journal of nanomedicine Vol. 15; pp. 17 - 29
• Main Authors: Hsiao, Yai-Ping, Chen, Hui-Ting, Liang, Yu-Chih, Wang, Tse-En, Huang, Kai-Hung, Hsu, Cheng-Chih, Liang, Hong-Jen, Huang, Chung-Hsiung, Jan, Tong-Rong
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2020; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Bioavailability; Biphenyl Compounds - administration & dosage; Cytokines; Disease; Diseases; Drug delivery systems; Drug Delivery Systems - methods; Drug dosages; Efficiency; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - etiology; Ethanol; experimental autoimmune encephalomyelitis; Female; Fingolimod; honokiol; Inflammation; Injections, Intravenous; Laboratory animals; Lignans - administration & dosage; Lipids; Mice, Inbred C57BL; Microglia - drug effects; Microglia - pathology; Multiple sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis - etiology; Myelitis - drug therapy; Myelitis - etiology; nanosome; Nanostructures - administration & dosage; Nanostructures - chemistry; neuroinflammation; Neuroprotective Agents - pharmacology; Novels; Original Research; Paralysis; Phospholipids; Phytochemicals; Spinal Cord - pathology; Th1 Cells - drug effects; Th1 Cells - pathology; ultra-high pressure homogenization; Vehicles; Taiwan; California; United States > US; Massachusetts; ultra-high pressure homogenization; honokiol; experimental autoimmune encephalomyelitis; nanosome; neuroinflammation
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S214349

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. 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. 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. 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-γ cells infiltrating the spinal cord. 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.