Development of nanosome-encapsulated honokiol for intravenous therapy against experimental autoimmune encephalomyelitis
Journal
International Journal of Nanomedicine
Journal Volume
15
Pages
17-29
Date Issued
2020
Author(s)
Hsiao, Y.-P.
Chen, H.-T.
Liang, Y.-C.
Wang, T.-E.
Huang, K.-H.
Hsu, C.-C.
Liang, H.-J.
Huang, C.-H.
Abstract
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-γ+ 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. ? 2020 Hsiao et al.
SDGs
Other Subjects
honokiol; nanoparticle; nanosome; unclassified drug; antiinflammatory agent; biphenyl derivative; honokiol; lignan; nanomaterial; neuroprotective agent; animal experiment; animal model; Article; controlled study; drug formulation; experimental autoimmune encephalomyelitis; female; mouse; multiple sclerosis; nanoencapsulation; nonhuman; animal; C57BL mouse; chemistry; drug delivery system; drug effect; experimental autoimmune encephalomyelitis; intravenous drug administration; microglia; multiple sclerosis; myelitis; pathology; procedures; spinal cord; Th1 cell; Animals; Anti-Inflammatory Agents; Biphenyl Compounds; Drug Delivery Systems; Encephalomyelitis, Autoimmune, Experimental; Female; Injections, Intravenous; Lignans; Mice, Inbred C57BL; Microglia; Multiple Sclerosis; Myelitis; Nanostructures; Neuroprotective Agents; Spinal Cord; Th1 Cells
Type
journal article