Development of Nanosome-Encapsulated Honokiol for Intravenous Therapy Against Experimental Autoimmune Encephalomyelitis
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 intravenou...
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| Published in | International journal of nanomedicine Vol. 15; pp. 17 - 29 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
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Dove Medical Press Limited
01.01.2020
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| Abstract | 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. |
|---|---|
| AbstractList | 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. Yai-Ping Hsiao,1 Hui-Ting Chen,1 Yu-Chih Liang,2 Tse-En Wang,1 Kai-Hung Huang,3 Cheng-Chih Hsu,3 Hong-Jen Liang,4 Chung-Hsiung Huang,5 Tong-Rong Jan1 1Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei 10617, Taiwan; 2School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 10617, Taiwan; 3Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan; 4Department of Food Science, Yuanpei University, Hsinchu 30015, Taiwan; 5Department of Food Science, National Taiwan Ocean University, Keelung 20224, TaiwanCorrespondence: Tong-Rong JanDepartment and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No.1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan, ROCTel +886-2-33661287Fax +886-2-23661475Email tonyjan@ntu.edu.twChung-Hsiung HuangDepartment of Food Science, National Taiwan Ocean University, No.2, Beining Road, Keelung 20224, TaiwanTel +886-2-24622192#5115Email huangch@mail.ntou.edu.twBackground: 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.Keywords: experimental autoimmune encephalomyelitis, honokiol, nanosome, neuroinflammation, ultra-high pressure homogenization 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. 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 [+ or -] 0.1 nm and the encapsulation efficiency 58.1 [+ or -] 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.sup.+], Iba-[1.sup.+][TNF.sup.+], Iba-[1.sup.+]IL-12 p[40.sup.+], and CD[3.sup.+]IFN-[[gamma].sup.+] 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. Keywords: experimental autoimmune encephalomyelitis, honokiol, nanosome, neuroinflammation, ultra-high pressure homogenization 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.BACKGROUNDHonokiol 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.PURPOSEThis 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.METHODSNanosomes 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.RESULTSThe 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.CONCLUSIONThe 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. |
| Audience | Academic |
| Author | Liang, Hong-Jen Hsiao, Yai-Ping Wang, Tse-En Huang, Chung-Hsiung Jan, Tong-Rong Hsu, Cheng-Chih Chen, Hui-Ting Huang, Kai-Hung Liang, Yu-Chih |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32021162$$D View this record in MEDLINE/PubMed |
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| Keywords | ultra-high pressure homogenization honokiol experimental autoimmune encephalomyelitis nanosome neuroinflammation |
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| Snippet | Honokiol has been reported to possess anti-inflammatory and neuroprotective activities. However, the poor aqueous solubility of honokiol limits its clinical... Background: Honokiol has been reported to possess anti-inflammatory and neuroprotective activities. However, the poor aqueous solubility of honokiol limits its... Yai-Ping Hsiao,1 Hui-Ting Chen,1 Yu-Chih Liang,2 Tse-En Wang,1 Kai-Hung Huang,3 Cheng-Chih Hsu,3 Hong-Jen Liang,4 Chung-Hsiung Huang,5 Tong-Rong Jan1... |
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| SubjectTerms | 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 |
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| Title | Development of Nanosome-Encapsulated Honokiol for Intravenous Therapy Against Experimental Autoimmune Encephalomyelitis |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/32021162 https://www.proquest.com/docview/2340004722 https://www.proquest.com/docview/2351486844 https://pubmed.ncbi.nlm.nih.gov/PMC6954093 https://doaj.org/article/30eb5c5173cc4b7684bf86974bc0b784 |
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