CDX-modified chitosan nanoparticles remarkably reduce therapeutic dose of fingolimod in the EAE model of mice
[Display omitted] Fingolimod (Fin), an FDA-approved drug, is used to control relapsing-remitting multiple sclerosis (MS). This therapeutic agent faces crucial drawbacks like poor bioavailability rate, risk of cardiotoxicity, potent immunosuppressive effects, and high cost. Here, we aimed to assess t...
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| Veröffentlicht in: | International journal of pharmaceutics 2023-04, Vol.636, p.122815-122815, Article 122815 |
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| container_title | International journal of pharmaceutics |
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| creator | Sepasi, Tina Ghadiri, Tahereh Ebrahimi-Kalan, Abbas Bani, Farhad Talebi, Mehdi Rahbarghazi, Reza Khodakarimi, Sina Beyrampour-Basmenj, Hanieh Seidi, Khaled Abbaspour-Ravasjani, Soheil Sadeghi, Mohammad-Reza Zarebkohan, Amir Gao, Huile |
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Fingolimod (Fin), an FDA-approved drug, is used to control relapsing-remitting multiple sclerosis (MS). This therapeutic agent faces crucial drawbacks like poor bioavailability rate, risk of cardiotoxicity, potent immunosuppressive effects, and high cost. Here, we aimed to assess the therapeutic efficacy of nano-formulated Fin in a mouse model of experimental autoimmune encephalomyelitis (EAE). Results showed the suitability of the present protocol in the synthesis of Fin-loaded CDX-modified chitosan (CS) nanoparticles (NPs) (Fin@CSCDX) with suitable physicochemical features. Confocal microscopy confirmed the appropriate accumulation of synthesized NPs within the brain parenchyma. Compared to the control EAE mice, INF-γ levels were significantly reduced in the group that received Fin@CSCDX (p |
| doi_str_mv | 10.1016/j.ijpharm.2023.122815 |
| format | Article |
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Fingolimod (Fin), an FDA-approved drug, is used to control relapsing-remitting multiple sclerosis (MS). This therapeutic agent faces crucial drawbacks like poor bioavailability rate, risk of cardiotoxicity, potent immunosuppressive effects, and high cost. Here, we aimed to assess the therapeutic efficacy of nano-formulated Fin in a mouse model of experimental autoimmune encephalomyelitis (EAE). Results showed the suitability of the present protocol in the synthesis of Fin-loaded CDX-modified chitosan (CS) nanoparticles (NPs) (Fin@CSCDX) with suitable physicochemical features. Confocal microscopy confirmed the appropriate accumulation of synthesized NPs within the brain parenchyma. Compared to the control EAE mice, INF-γ levels were significantly reduced in the group that received Fin@CSCDX (p < 0.05). Along with these data, Fin@CSCDX reduced the expression of TBX21, GATA3, FOXP3, and Rorc associated with the auto-reactivation of T cells (p < 0.05). Histological examination indicated a low-rate lymphocyte infiltration into the spinal cord parenchyma after the administration of Fin@CSCDX. Of note, HPLC data revealed that the concentration of nano-formulated Fin was about 15-fold less than Fin therapeutic doses (TD) with similar reparative effects. Neurological scores were similar in both groups that received nano-formulated fingolimod 1/15th of free Fin therapeutic amounts. Fluorescence imaging indicated that macrophages and especially microglia can efficiently uptake Fin@CSCDX NPs, leading to the regulation of pro-inflammatory responses. Taken together, current results indicated that CDX-modified CS NPs provide a suitable platform not only for the efficient reduction of Fin TD but also these NPs can target the brain immune cells during neurodegenerative disorders.</description><identifier>ISSN: 0378-5173</identifier><identifier>EISSN: 1873-3476</identifier><identifier>DOI: 10.1016/j.ijpharm.2023.122815</identifier><identifier>PMID: 36907279</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; CDX ; Chitosan - therapeutic use ; Chitosan nanoparticles ; Encephalomyelitis ; Encephalomyelitis, Autoimmune, Experimental - drug therapy ; Encephalomyelitis, Autoimmune, Experimental - metabolism ; Experimental autoimmune ; Fingolimod ; Fingolimod Hydrochloride - therapeutic use ; Mice ; Mice, Inbred C57BL ; Nanoparticles ; T-Lymphocytes - metabolism ; Targeted delivery</subject><ispartof>International journal of pharmaceutics, 2023-04, Vol.636, p.122815-122815, Article 122815</ispartof><rights>2023 Elsevier B.V.</rights><rights>Copyright © 2023 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-7d1d70aa5cdf13ee0a7cc8f553e817e0a16c630b5b892fffae4005132e8a33da3</citedby><cites>FETCH-LOGICAL-c365t-7d1d70aa5cdf13ee0a7cc8f553e817e0a16c630b5b892fffae4005132e8a33da3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378517323002351$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36907279$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sepasi, Tina</creatorcontrib><creatorcontrib>Ghadiri, Tahereh</creatorcontrib><creatorcontrib>Ebrahimi-Kalan, Abbas</creatorcontrib><creatorcontrib>Bani, Farhad</creatorcontrib><creatorcontrib>Talebi, Mehdi</creatorcontrib><creatorcontrib>Rahbarghazi, Reza</creatorcontrib><creatorcontrib>Khodakarimi, Sina</creatorcontrib><creatorcontrib>Beyrampour-Basmenj, Hanieh</creatorcontrib><creatorcontrib>Seidi, Khaled</creatorcontrib><creatorcontrib>Abbaspour-Ravasjani, Soheil</creatorcontrib><creatorcontrib>Sadeghi, Mohammad-Reza</creatorcontrib><creatorcontrib>Zarebkohan, Amir</creatorcontrib><creatorcontrib>Gao, Huile</creatorcontrib><title>CDX-modified chitosan nanoparticles remarkably reduce therapeutic dose of fingolimod in the EAE model of mice</title><title>International journal of pharmaceutics</title><addtitle>Int J Pharm</addtitle><description>[Display omitted]
Fingolimod (Fin), an FDA-approved drug, is used to control relapsing-remitting multiple sclerosis (MS). This therapeutic agent faces crucial drawbacks like poor bioavailability rate, risk of cardiotoxicity, potent immunosuppressive effects, and high cost. Here, we aimed to assess the therapeutic efficacy of nano-formulated Fin in a mouse model of experimental autoimmune encephalomyelitis (EAE). Results showed the suitability of the present protocol in the synthesis of Fin-loaded CDX-modified chitosan (CS) nanoparticles (NPs) (Fin@CSCDX) with suitable physicochemical features. Confocal microscopy confirmed the appropriate accumulation of synthesized NPs within the brain parenchyma. Compared to the control EAE mice, INF-γ levels were significantly reduced in the group that received Fin@CSCDX (p < 0.05). Along with these data, Fin@CSCDX reduced the expression of TBX21, GATA3, FOXP3, and Rorc associated with the auto-reactivation of T cells (p < 0.05). Histological examination indicated a low-rate lymphocyte infiltration into the spinal cord parenchyma after the administration of Fin@CSCDX. Of note, HPLC data revealed that the concentration of nano-formulated Fin was about 15-fold less than Fin therapeutic doses (TD) with similar reparative effects. Neurological scores were similar in both groups that received nano-formulated fingolimod 1/15th of free Fin therapeutic amounts. Fluorescence imaging indicated that macrophages and especially microglia can efficiently uptake Fin@CSCDX NPs, leading to the regulation of pro-inflammatory responses. Taken together, current results indicated that CDX-modified CS NPs provide a suitable platform not only for the efficient reduction of Fin TD but also these NPs can target the brain immune cells during neurodegenerative disorders.</description><subject>Animals</subject><subject>CDX</subject><subject>Chitosan - therapeutic use</subject><subject>Chitosan nanoparticles</subject><subject>Encephalomyelitis</subject><subject>Encephalomyelitis, Autoimmune, Experimental - drug therapy</subject><subject>Encephalomyelitis, Autoimmune, Experimental - metabolism</subject><subject>Experimental autoimmune</subject><subject>Fingolimod</subject><subject>Fingolimod Hydrochloride - therapeutic use</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Nanoparticles</subject><subject>T-Lymphocytes - metabolism</subject><subject>Targeted delivery</subject><issn>0378-5173</issn><issn>1873-3476</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1PGzEQQC1UBGngJxT52Mum_sD25oRQCAUpUi8gcbO89pg43V0v9i4S_x5HCb32NDOaNzOah9APShaUUPlrtwi7YWtSt2CE8QVlrKbiBM1orXjFr5X8hmaEq7oSVPFz9D3nHSFEMsrP0DmXS6KYWs5Qt7p7qbrogg_gsN2GMWbT4970cTBpDLaFjBN0Jv01TftRUjdZwOMWkhlgKgB2MQOOHvvQv8Y2lGU49HsCr2_XuJTQ7ttdsHCBTr1pM1we4xw936-fVg_V5s_vx9XtprJcirFSjjpFjBHWecoBiFHW1l4IDjVVpaTSSk4a0dRL5r03cE2IoJxBbTh3hs_Rz8PeIcW3CfKou5AttK3pIU5ZM1XLwkvKCioOqE0x5wReDymUdz80JXpvWu_00bTem9YH02Xu6nhiajpw_6a-1Bbg5gBAefQ9QNLZBugtuJDAjtrF8J8Tn99skzk</recordid><startdate>20230405</startdate><enddate>20230405</enddate><creator>Sepasi, Tina</creator><creator>Ghadiri, Tahereh</creator><creator>Ebrahimi-Kalan, Abbas</creator><creator>Bani, Farhad</creator><creator>Talebi, Mehdi</creator><creator>Rahbarghazi, Reza</creator><creator>Khodakarimi, Sina</creator><creator>Beyrampour-Basmenj, Hanieh</creator><creator>Seidi, Khaled</creator><creator>Abbaspour-Ravasjani, Soheil</creator><creator>Sadeghi, Mohammad-Reza</creator><creator>Zarebkohan, Amir</creator><creator>Gao, Huile</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20230405</creationdate><title>CDX-modified chitosan nanoparticles remarkably reduce therapeutic dose of fingolimod in the EAE model of mice</title><author>Sepasi, Tina ; Ghadiri, Tahereh ; Ebrahimi-Kalan, Abbas ; Bani, Farhad ; Talebi, Mehdi ; Rahbarghazi, Reza ; Khodakarimi, Sina ; Beyrampour-Basmenj, Hanieh ; Seidi, Khaled ; Abbaspour-Ravasjani, Soheil ; Sadeghi, Mohammad-Reza ; Zarebkohan, Amir ; Gao, Huile</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-7d1d70aa5cdf13ee0a7cc8f553e817e0a16c630b5b892fffae4005132e8a33da3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>CDX</topic><topic>Chitosan - therapeutic use</topic><topic>Chitosan nanoparticles</topic><topic>Encephalomyelitis</topic><topic>Encephalomyelitis, Autoimmune, Experimental - drug therapy</topic><topic>Encephalomyelitis, Autoimmune, Experimental - metabolism</topic><topic>Experimental autoimmune</topic><topic>Fingolimod</topic><topic>Fingolimod Hydrochloride - therapeutic use</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Nanoparticles</topic><topic>T-Lymphocytes - metabolism</topic><topic>Targeted delivery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sepasi, Tina</creatorcontrib><creatorcontrib>Ghadiri, Tahereh</creatorcontrib><creatorcontrib>Ebrahimi-Kalan, Abbas</creatorcontrib><creatorcontrib>Bani, Farhad</creatorcontrib><creatorcontrib>Talebi, Mehdi</creatorcontrib><creatorcontrib>Rahbarghazi, Reza</creatorcontrib><creatorcontrib>Khodakarimi, Sina</creatorcontrib><creatorcontrib>Beyrampour-Basmenj, Hanieh</creatorcontrib><creatorcontrib>Seidi, Khaled</creatorcontrib><creatorcontrib>Abbaspour-Ravasjani, Soheil</creatorcontrib><creatorcontrib>Sadeghi, Mohammad-Reza</creatorcontrib><creatorcontrib>Zarebkohan, Amir</creatorcontrib><creatorcontrib>Gao, Huile</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sepasi, Tina</au><au>Ghadiri, Tahereh</au><au>Ebrahimi-Kalan, Abbas</au><au>Bani, Farhad</au><au>Talebi, Mehdi</au><au>Rahbarghazi, Reza</au><au>Khodakarimi, Sina</au><au>Beyrampour-Basmenj, Hanieh</au><au>Seidi, Khaled</au><au>Abbaspour-Ravasjani, Soheil</au><au>Sadeghi, Mohammad-Reza</au><au>Zarebkohan, Amir</au><au>Gao, Huile</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CDX-modified chitosan nanoparticles remarkably reduce therapeutic dose of fingolimod in the EAE model of mice</atitle><jtitle>International journal of pharmaceutics</jtitle><addtitle>Int J Pharm</addtitle><date>2023-04-05</date><risdate>2023</risdate><volume>636</volume><spage>122815</spage><epage>122815</epage><pages>122815-122815</pages><artnum>122815</artnum><issn>0378-5173</issn><eissn>1873-3476</eissn><abstract>[Display omitted]
Fingolimod (Fin), an FDA-approved drug, is used to control relapsing-remitting multiple sclerosis (MS). This therapeutic agent faces crucial drawbacks like poor bioavailability rate, risk of cardiotoxicity, potent immunosuppressive effects, and high cost. Here, we aimed to assess the therapeutic efficacy of nano-formulated Fin in a mouse model of experimental autoimmune encephalomyelitis (EAE). Results showed the suitability of the present protocol in the synthesis of Fin-loaded CDX-modified chitosan (CS) nanoparticles (NPs) (Fin@CSCDX) with suitable physicochemical features. Confocal microscopy confirmed the appropriate accumulation of synthesized NPs within the brain parenchyma. Compared to the control EAE mice, INF-γ levels were significantly reduced in the group that received Fin@CSCDX (p < 0.05). Along with these data, Fin@CSCDX reduced the expression of TBX21, GATA3, FOXP3, and Rorc associated with the auto-reactivation of T cells (p < 0.05). Histological examination indicated a low-rate lymphocyte infiltration into the spinal cord parenchyma after the administration of Fin@CSCDX. Of note, HPLC data revealed that the concentration of nano-formulated Fin was about 15-fold less than Fin therapeutic doses (TD) with similar reparative effects. Neurological scores were similar in both groups that received nano-formulated fingolimod 1/15th of free Fin therapeutic amounts. Fluorescence imaging indicated that macrophages and especially microglia can efficiently uptake Fin@CSCDX NPs, leading to the regulation of pro-inflammatory responses. Taken together, current results indicated that CDX-modified CS NPs provide a suitable platform not only for the efficient reduction of Fin TD but also these NPs can target the brain immune cells during neurodegenerative disorders.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>36907279</pmid><doi>10.1016/j.ijpharm.2023.122815</doi><tpages>1</tpages></addata></record> |
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| subjects | Animals CDX Chitosan - therapeutic use Chitosan nanoparticles Encephalomyelitis Encephalomyelitis, Autoimmune, Experimental - drug therapy Encephalomyelitis, Autoimmune, Experimental - metabolism Experimental autoimmune Fingolimod Fingolimod Hydrochloride - therapeutic use Mice Mice, Inbred C57BL Nanoparticles T-Lymphocytes - metabolism Targeted delivery |
| title | CDX-modified chitosan nanoparticles remarkably reduce therapeutic dose of fingolimod in the EAE model of mice |
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