Calcium ion coordinated dexamethasone supramolecular hydrogel as therapeutic alternative for control of non-infectious uveitis
[Display omitted] Supramolecular hydrogels formed by the self-assembly of therapeutic agents have received considerable attention due to their high drug payload and carrier-free features. Herein, we constructed a dexamethasone sodium phosphate (Dex) supramolecular hydrogel in combination with Dex an...
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| Veröffentlicht in: | Acta biomaterialia 2017-10, Vol.61, p.157-168 |
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| creator | Wu, Wei Zhang, Zhaoliang Xiong, Taotao Zhao, Wenguang Jiang, Rou Chen, Hao Li, Xingyi |
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Supramolecular hydrogels formed by the self-assembly of therapeutic agents have received considerable attention due to their high drug payload and carrier-free features. Herein, we constructed a dexamethasone sodium phosphate (Dex) supramolecular hydrogel in combination with Dex and calcium ion (Ca2+) and further demonstrated its therapeutic efficacy in the control of ocular inflammation. The developed supramolecular hydrogel was thoroughly characterized by rheology, TEM, FTIR and XRD. Calcium ions and Dex concentration had a marked influence on the sol-gel transition behaviour of hydrogel and the proposed Dex supramolecular hydrogel displayed thixotropic properties. The drug release rate from Dex supramolecular hydrogel was dependent on the Ca2+ concentration. In comparison with Dex aqueous solution, single intravitreal injections of Dex supramolecular hydrogel up to 30μg/eye were well tolerated without causing undesirable complications of fundus blood vessel tortuosity and lens opacity, as indicated by electroretinograms (ERGs), fundus photography and histopathology. Moreover, the administration by Dex supramolecular hydrogel exhibited a comparable anti-inflammatory efficacy to native Dex solution on an experimental autoimmune uveitis (EAU) model induced in Lewis rats with IRBP peptide and the therapeutic efficacy had in a dosage-dependent manner. Histological observation and cytokines measurements indicated that both Dex solution and Dex supramolecular hydrogel (30μg/eye) treatment could significantly attenuate the inflammatory response in both anterior and posterior chambers via the downregulation of Th1 and Th17 effector responses. All these data suggested that the developed Dex supramolecular hydrogel might be a therapeutic alternative for non-infectious uveitis with minimal risk of the induction of lens opacity and fundus blood vessel tortuosity.
A facile ionic cross-linking strategy was exploited to construct a dexamethasone sodium phosphate (Dex) supramolecular hydrogel composed of Dex and calcium ion. Intravitreal injection of Dex hydrogel displayed excellent intraocular biocompatibility without causing the complications of fundus blood vessel tortuosity and lens opacity. More importantly, the proposed Dex hydrogel exhibited a comparative anti-inflammatory response to native Dex formulation on an experimental autoimmune uveitis (EAU) model via the downregulation of Th1 and Th17 effector responses. |
| doi_str_mv | 10.1016/j.actbio.2017.05.024 |
| format | Article |
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Supramolecular hydrogels formed by the self-assembly of therapeutic agents have received considerable attention due to their high drug payload and carrier-free features. Herein, we constructed a dexamethasone sodium phosphate (Dex) supramolecular hydrogel in combination with Dex and calcium ion (Ca2+) and further demonstrated its therapeutic efficacy in the control of ocular inflammation. The developed supramolecular hydrogel was thoroughly characterized by rheology, TEM, FTIR and XRD. Calcium ions and Dex concentration had a marked influence on the sol-gel transition behaviour of hydrogel and the proposed Dex supramolecular hydrogel displayed thixotropic properties. The drug release rate from Dex supramolecular hydrogel was dependent on the Ca2+ concentration. In comparison with Dex aqueous solution, single intravitreal injections of Dex supramolecular hydrogel up to 30μg/eye were well tolerated without causing undesirable complications of fundus blood vessel tortuosity and lens opacity, as indicated by electroretinograms (ERGs), fundus photography and histopathology. Moreover, the administration by Dex supramolecular hydrogel exhibited a comparable anti-inflammatory efficacy to native Dex solution on an experimental autoimmune uveitis (EAU) model induced in Lewis rats with IRBP peptide and the therapeutic efficacy had in a dosage-dependent manner. Histological observation and cytokines measurements indicated that both Dex solution and Dex supramolecular hydrogel (30μg/eye) treatment could significantly attenuate the inflammatory response in both anterior and posterior chambers via the downregulation of Th1 and Th17 effector responses. All these data suggested that the developed Dex supramolecular hydrogel might be a therapeutic alternative for non-infectious uveitis with minimal risk of the induction of lens opacity and fundus blood vessel tortuosity.
A facile ionic cross-linking strategy was exploited to construct a dexamethasone sodium phosphate (Dex) supramolecular hydrogel composed of Dex and calcium ion. Intravitreal injection of Dex hydrogel displayed excellent intraocular biocompatibility without causing the complications of fundus blood vessel tortuosity and lens opacity. More importantly, the proposed Dex hydrogel exhibited a comparative anti-inflammatory response to native Dex formulation on an experimental autoimmune uveitis (EAU) model via the downregulation of Th1 and Th17 effector responses.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2017.05.024</identifier><identifier>PMID: 28501709</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Anti-inflammatory ; Biocompatible Materials - chemistry ; Blood vessels ; Calcium ; Calcium - chemistry ; Calcium ions ; Chemical compounds ; Complications ; Cytokines ; Cytokines - metabolism ; Dexamethasone ; Dexamethasone - chemistry ; Dexamethasone - pharmacology ; Dexamethasone - therapeutic use ; Drug delivery systems ; Drug Liberation ; Effectiveness ; Electroretinograms ; Experimental autoimmune uveitis ; Experimental autoimmune uveoretinitis ; Eye ; Eye lens ; Helper cells ; Histopathology ; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry ; Hydrogels ; In vivo ; Infectious diseases ; Inflammation ; Inflammatory response ; Interphotoreceptor retinoid-binding protein ; Ions ; Lymphocytes T ; Male ; Opacity ; Peptides ; Pharmacology ; Phase Transition ; Phosphates ; Photography ; Rats ; Rats, Inbred Lew ; Rats, Sprague-Dawley ; Retina - drug effects ; Retina - pathology ; Rheological properties ; Rheology ; Self-assembly ; Sodium ; Sodium phosphate ; Sol-gel processes ; Supramolecular hydrogel ; Tortuosity ; Uveitis ; Uveitis - drug therapy ; Uveitis - pathology ; X-Ray Diffraction</subject><ispartof>Acta biomaterialia, 2017-10, Vol.61, p.157-168</ispartof><rights>2017 Acta Materialia Inc.</rights><rights>Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier BV Oct 1, 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-346707b7d0678a3b169b5959e876ea0009af99ce091518255eb8cccda6bbd38f3</citedby><cites>FETCH-LOGICAL-c456t-346707b7d0678a3b169b5959e876ea0009af99ce091518255eb8cccda6bbd38f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.actbio.2017.05.024$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28501709$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Wei</creatorcontrib><creatorcontrib>Zhang, Zhaoliang</creatorcontrib><creatorcontrib>Xiong, Taotao</creatorcontrib><creatorcontrib>Zhao, Wenguang</creatorcontrib><creatorcontrib>Jiang, Rou</creatorcontrib><creatorcontrib>Chen, Hao</creatorcontrib><creatorcontrib>Li, Xingyi</creatorcontrib><title>Calcium ion coordinated dexamethasone supramolecular hydrogel as therapeutic alternative for control of non-infectious uveitis</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>[Display omitted]
Supramolecular hydrogels formed by the self-assembly of therapeutic agents have received considerable attention due to their high drug payload and carrier-free features. Herein, we constructed a dexamethasone sodium phosphate (Dex) supramolecular hydrogel in combination with Dex and calcium ion (Ca2+) and further demonstrated its therapeutic efficacy in the control of ocular inflammation. The developed supramolecular hydrogel was thoroughly characterized by rheology, TEM, FTIR and XRD. Calcium ions and Dex concentration had a marked influence on the sol-gel transition behaviour of hydrogel and the proposed Dex supramolecular hydrogel displayed thixotropic properties. The drug release rate from Dex supramolecular hydrogel was dependent on the Ca2+ concentration. In comparison with Dex aqueous solution, single intravitreal injections of Dex supramolecular hydrogel up to 30μg/eye were well tolerated without causing undesirable complications of fundus blood vessel tortuosity and lens opacity, as indicated by electroretinograms (ERGs), fundus photography and histopathology. Moreover, the administration by Dex supramolecular hydrogel exhibited a comparable anti-inflammatory efficacy to native Dex solution on an experimental autoimmune uveitis (EAU) model induced in Lewis rats with IRBP peptide and the therapeutic efficacy had in a dosage-dependent manner. Histological observation and cytokines measurements indicated that both Dex solution and Dex supramolecular hydrogel (30μg/eye) treatment could significantly attenuate the inflammatory response in both anterior and posterior chambers via the downregulation of Th1 and Th17 effector responses. All these data suggested that the developed Dex supramolecular hydrogel might be a therapeutic alternative for non-infectious uveitis with minimal risk of the induction of lens opacity and fundus blood vessel tortuosity.
A facile ionic cross-linking strategy was exploited to construct a dexamethasone sodium phosphate (Dex) supramolecular hydrogel composed of Dex and calcium ion. Intravitreal injection of Dex hydrogel displayed excellent intraocular biocompatibility without causing the complications of fundus blood vessel tortuosity and lens opacity. More importantly, the proposed Dex hydrogel exhibited a comparative anti-inflammatory response to native Dex formulation on an experimental autoimmune uveitis (EAU) model via the downregulation of Th1 and Th17 effector responses.</description><subject>Animals</subject><subject>Anti-inflammatory</subject><subject>Biocompatible Materials - chemistry</subject><subject>Blood vessels</subject><subject>Calcium</subject><subject>Calcium - chemistry</subject><subject>Calcium ions</subject><subject>Chemical compounds</subject><subject>Complications</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Dexamethasone</subject><subject>Dexamethasone - chemistry</subject><subject>Dexamethasone - pharmacology</subject><subject>Dexamethasone - therapeutic use</subject><subject>Drug delivery systems</subject><subject>Drug Liberation</subject><subject>Effectiveness</subject><subject>Electroretinograms</subject><subject>Experimental autoimmune uveitis</subject><subject>Experimental autoimmune uveoretinitis</subject><subject>Eye</subject><subject>Eye lens</subject><subject>Helper cells</subject><subject>Histopathology</subject><subject>Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry</subject><subject>Hydrogels</subject><subject>In vivo</subject><subject>Infectious diseases</subject><subject>Inflammation</subject><subject>Inflammatory response</subject><subject>Interphotoreceptor retinoid-binding protein</subject><subject>Ions</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Opacity</subject><subject>Peptides</subject><subject>Pharmacology</subject><subject>Phase Transition</subject><subject>Phosphates</subject><subject>Photography</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>Rats, Sprague-Dawley</subject><subject>Retina - drug effects</subject><subject>Retina - pathology</subject><subject>Rheological properties</subject><subject>Rheology</subject><subject>Self-assembly</subject><subject>Sodium</subject><subject>Sodium phosphate</subject><subject>Sol-gel processes</subject><subject>Supramolecular hydrogel</subject><subject>Tortuosity</subject><subject>Uveitis</subject><subject>Uveitis - drug therapy</subject><subject>Uveitis - pathology</subject><subject>X-Ray Diffraction</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kTuP1DAUhSMEYh_wDxCyREOTYCfxq0FCI2CRVqKB2nLsG8Yjxx78GO02_Ha8moWCgsq3-M65vud03SuCB4IJe3cYtCmLi8OICR8wHfA4P-kuieCi55SJp23m89hzzMhFd5XzAeNJkFE87y5GQZsIy8vu10574-qGXAzIxJisC7qARRbu9AZlr3MMgHI9Jr1FD6Z6ndD-3qb4AzzSGZU9JH2EWpxB2hdITe9OgNaYmmEoKXoUVxRi6F1YwRQXa0b1BK64_KJ7tmqf4eXje919__Tx2-6mv_36-cvuw21vZspKP82MY75wixkXeloIkwuVVILgDDTGWOpVSgNYEkrESCkswhhjNVsWO4l1uu7enn2PKf6skIvaXDbgvQ7QvqOIkJKQSWDa0Df_oIdY21G-UZLNtMXNxkbNZ8qkmHOCVR2T23S6VwSrh37UQZ37UQ_9KExV66fJXj-a12UD-1f0p5AGvD8D0NI4OUgqGwfBgHWpZadsdP_f8BsZ0qW0</recordid><startdate>20171001</startdate><enddate>20171001</enddate><creator>Wu, Wei</creator><creator>Zhang, Zhaoliang</creator><creator>Xiong, Taotao</creator><creator>Zhao, Wenguang</creator><creator>Jiang, Rou</creator><creator>Chen, Hao</creator><creator>Li, Xingyi</creator><general>Elsevier Ltd</general><general>Elsevier BV</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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20171001</creationdate><title>Calcium ion coordinated dexamethasone supramolecular hydrogel as therapeutic alternative for control of non-infectious uveitis</title><author>Wu, Wei ; Zhang, Zhaoliang ; Xiong, Taotao ; Zhao, Wenguang ; Jiang, Rou ; Chen, Hao ; Li, Xingyi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-346707b7d0678a3b169b5959e876ea0009af99ce091518255eb8cccda6bbd38f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Anti-inflammatory</topic><topic>Biocompatible Materials - 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drug effects</topic><topic>Retina - pathology</topic><topic>Rheological properties</topic><topic>Rheology</topic><topic>Self-assembly</topic><topic>Sodium</topic><topic>Sodium phosphate</topic><topic>Sol-gel processes</topic><topic>Supramolecular hydrogel</topic><topic>Tortuosity</topic><topic>Uveitis</topic><topic>Uveitis - drug therapy</topic><topic>Uveitis - pathology</topic><topic>X-Ray Diffraction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Wei</creatorcontrib><creatorcontrib>Zhang, Zhaoliang</creatorcontrib><creatorcontrib>Xiong, Taotao</creatorcontrib><creatorcontrib>Zhao, Wenguang</creatorcontrib><creatorcontrib>Jiang, Rou</creatorcontrib><creatorcontrib>Chen, Hao</creatorcontrib><creatorcontrib>Li, Xingyi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Acta biomaterialia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Wei</au><au>Zhang, Zhaoliang</au><au>Xiong, Taotao</au><au>Zhao, Wenguang</au><au>Jiang, Rou</au><au>Chen, Hao</au><au>Li, Xingyi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Calcium ion coordinated dexamethasone supramolecular hydrogel as therapeutic alternative for control of non-infectious uveitis</atitle><jtitle>Acta biomaterialia</jtitle><addtitle>Acta Biomater</addtitle><date>2017-10-01</date><risdate>2017</risdate><volume>61</volume><spage>157</spage><epage>168</epage><pages>157-168</pages><issn>1742-7061</issn><eissn>1878-7568</eissn><abstract>[Display omitted]
Supramolecular hydrogels formed by the self-assembly of therapeutic agents have received considerable attention due to their high drug payload and carrier-free features. Herein, we constructed a dexamethasone sodium phosphate (Dex) supramolecular hydrogel in combination with Dex and calcium ion (Ca2+) and further demonstrated its therapeutic efficacy in the control of ocular inflammation. The developed supramolecular hydrogel was thoroughly characterized by rheology, TEM, FTIR and XRD. Calcium ions and Dex concentration had a marked influence on the sol-gel transition behaviour of hydrogel and the proposed Dex supramolecular hydrogel displayed thixotropic properties. The drug release rate from Dex supramolecular hydrogel was dependent on the Ca2+ concentration. In comparison with Dex aqueous solution, single intravitreal injections of Dex supramolecular hydrogel up to 30μg/eye were well tolerated without causing undesirable complications of fundus blood vessel tortuosity and lens opacity, as indicated by electroretinograms (ERGs), fundus photography and histopathology. Moreover, the administration by Dex supramolecular hydrogel exhibited a comparable anti-inflammatory efficacy to native Dex solution on an experimental autoimmune uveitis (EAU) model induced in Lewis rats with IRBP peptide and the therapeutic efficacy had in a dosage-dependent manner. Histological observation and cytokines measurements indicated that both Dex solution and Dex supramolecular hydrogel (30μg/eye) treatment could significantly attenuate the inflammatory response in both anterior and posterior chambers via the downregulation of Th1 and Th17 effector responses. All these data suggested that the developed Dex supramolecular hydrogel might be a therapeutic alternative for non-infectious uveitis with minimal risk of the induction of lens opacity and fundus blood vessel tortuosity.
A facile ionic cross-linking strategy was exploited to construct a dexamethasone sodium phosphate (Dex) supramolecular hydrogel composed of Dex and calcium ion. Intravitreal injection of Dex hydrogel displayed excellent intraocular biocompatibility without causing the complications of fundus blood vessel tortuosity and lens opacity. More importantly, the proposed Dex hydrogel exhibited a comparative anti-inflammatory response to native Dex formulation on an experimental autoimmune uveitis (EAU) model via the downregulation of Th1 and Th17 effector responses.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28501709</pmid><doi>10.1016/j.actbio.2017.05.024</doi><tpages>12</tpages></addata></record> |
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| ispartof | Acta biomaterialia, 2017-10, Vol.61, p.157-168 |
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| subjects | Animals Anti-inflammatory Biocompatible Materials - chemistry Blood vessels Calcium Calcium - chemistry Calcium ions Chemical compounds Complications Cytokines Cytokines - metabolism Dexamethasone Dexamethasone - chemistry Dexamethasone - pharmacology Dexamethasone - therapeutic use Drug delivery systems Drug Liberation Effectiveness Electroretinograms Experimental autoimmune uveitis Experimental autoimmune uveoretinitis Eye Eye lens Helper cells Histopathology Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry Hydrogels In vivo Infectious diseases Inflammation Inflammatory response Interphotoreceptor retinoid-binding protein Ions Lymphocytes T Male Opacity Peptides Pharmacology Phase Transition Phosphates Photography Rats Rats, Inbred Lew Rats, Sprague-Dawley Retina - drug effects Retina - pathology Rheological properties Rheology Self-assembly Sodium Sodium phosphate Sol-gel processes Supramolecular hydrogel Tortuosity Uveitis Uveitis - drug therapy Uveitis - pathology X-Ray Diffraction |
| title | Calcium ion coordinated dexamethasone supramolecular hydrogel as therapeutic alternative for control of non-infectious uveitis |
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