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Routes of Administration and Dose Optimization of Soluble Antigen Arrays in Mice with Experimental Autoimmune Encephalomyelitis
dc.contributor.author | Thati, Shara | |
dc.contributor.author | Kuehl, Christopher | |
dc.contributor.author | Hartwell, Brittany | |
dc.contributor.author | Sestak, Joshua | |
dc.contributor.author | Siahaan, Teruna J. | |
dc.contributor.author | Forrest, M. Laird | |
dc.contributor.author | Berkland, Cory J. | |
dc.date.accessioned | 2017-04-26T17:15:57Z | |
dc.date.available | 2017-04-26T17:15:57Z | |
dc.date.issued | 2015-02 | |
dc.identifier.citation | Thati, S., Kuehl, C., Hartwell, B., Sestak, J., Siahaan, T., Forrest, L., & Berkland, C. (2015). Routes of Administration and Dose Optimization of Soluble Antigen Arrays in Mice with Experimental Autoimmune Encephalomyelitis. Journal of Pharmaceutical Sciences, 104(2), 714–721. http://doi.org/10.1002/jps.24272 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23812 | |
dc.description.abstract | Soluble Antigen Arrays (SAgAs) were developed for treating mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. SAgAs are composed of hyaluronan with grafted EAE antigen and LABL peptide (a ligand of ICAM-1). SAgA dose was tested by varying injection volume, SAgA concentration, and administration schedule. Routes of administration were explored to determine the efficacy of SAgAs when injected intramuscularly, subcutaneously, intraperitoneally, intravenously, or instilled into lungs. Injections proximal to the central nervous system (CNS) were compared to distal injection sites. Intravenous dosing was included to determine if SAgA efficiency results from systemic exposure. Pulmonary instillation was included since reports suggest T cells are licensed in the lungs before moving onto the CNS1,2. Decreasing the volume of injection or SAgA dose reduced treatment efficacy. Treating mice with a single injection on day 4, 7, or 10 also reduced efficacy compared to injecting on all three days. Surprisingly, changing the injection site did not lead to a significant difference in efficacy. Intravenous administration showed efficacy similar to other routes, suggesting SAgAs act systemically. When SAgAs were delivered via pulmonary instillation, however, EAE mice failed to develop any symptoms, suggesting a unique lung mechanism to ameliorate EAE in mice. | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.subject | Hyaluronan | en_US |
dc.subject | Experimental autoimmune encephalomyelitis | en_US |
dc.subject | SJL mice | en_US |
dc.subject | HPLC | en_US |
dc.subject | Facilitated diffusion/transport; peptides | en_US |
dc.subject | Immunology | en_US |
dc.subject | Biomaterials | en_US |
dc.subject | Polymeric drug delivery system* | en_US |
dc.title | Routes of Administration and Dose Optimization of Soluble Antigen Arrays in Mice with Experimental Autoimmune Encephalomyelitis | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Thati, Shara | |
kusw.kuauthor | Kuehl, Christopher | |
kusw.kuauthor | Hartwell, Brittany | |
kusw.kuauthor | Sestak, Joshua | |
kusw.kuauthor | Siahaan, Teruna J. | |
kusw.kuauthor | Forrest, M. Laird | |
kusw.kuauthor | Berkland, Cory J. | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
kusw.kudepartment | Chemical and Petroleum Engineering | en_US |
dc.identifier.doi | 10.1002/jps.24272 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC4312227 | en_US |
dc.rights.accessrights | openAccess |
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Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.