Long‐term delivery of etanercept mediated via a thermosensitive hydrogel for efficient inhibition of wear debris‐induced inflammatory osteolysis
Periprosthetic wear debris‐induced aseptic loosening brings great pain to patients undergoing total joint arthroplasty. Tumor necrosis factor α (TNF‐α) is a pivotal cytokine involved in wear debris‐induced aseptic inflammation and subsequent osteolysis. Herein, we developed an injectable hydrogel sy...
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Veröffentlicht in: | Journal of polymer science (2020) 2022-10, Vol.60 (20), p.2875-2888 |
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description | Periprosthetic wear debris‐induced aseptic loosening brings great pain to patients undergoing total joint arthroplasty. Tumor necrosis factor α (TNF‐α) is a pivotal cytokine involved in wear debris‐induced aseptic inflammation and subsequent osteolysis. Herein, we developed an injectable hydrogel system containing etanercept (ETN), a TNF‐α antagonist, to inhibit wear debris‐induced osteolysis. A set of thermosensitive poly(lactide‐co‐glycolide)‐b‐poly(ethylene glycol)‐b‐poly(lactide‐co‐glycolide) (PLGA–PEG–PLGA) copolymers with comparable molecular weights but different LA/GA molar ratios were synthesized by us, and their aqueous solutions presented sol‐to‐gel transitions along with the elevation of temperature. The LA/GA ratio not only impacted the phase transition temperature but also controlled the degradation rate of gel in vivo. The hydrogel with an appropriate in vivo degradation rate was employed to load and deliver ETN, and the drug introduction did not influence on its thermo‐induced gelation behavior. The loaded ETN was released from the gel depot in vitro in a sustained manner for up to 30 days. In a mouse bone‐implanted air pouch model, a single injection of the hydrogel formulation and subsequent sustained release of active ETN efficiently neutralized TNF‐α, resulting in significant suppression of titanium particles‐induced aseptic inflammation and subsequent osteolysis, and the effect was pronouncedly superior to that of an ETN solution. |
doi_str_mv | 10.1002/pol.20220337 |
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Tumor necrosis factor α (TNF‐α) is a pivotal cytokine involved in wear debris‐induced aseptic inflammation and subsequent osteolysis. Herein, we developed an injectable hydrogel system containing etanercept (ETN), a TNF‐α antagonist, to inhibit wear debris‐induced osteolysis. A set of thermosensitive poly(lactide‐co‐glycolide)‐b‐poly(ethylene glycol)‐b‐poly(lactide‐co‐glycolide) (PLGA–PEG–PLGA) copolymers with comparable molecular weights but different LA/GA molar ratios were synthesized by us, and their aqueous solutions presented sol‐to‐gel transitions along with the elevation of temperature. The LA/GA ratio not only impacted the phase transition temperature but also controlled the degradation rate of gel in vivo. The hydrogel with an appropriate in vivo degradation rate was employed to load and deliver ETN, and the drug introduction did not influence on its thermo‐induced gelation behavior. The loaded ETN was released from the gel depot in vitro in a sustained manner for up to 30 days. In a mouse bone‐implanted air pouch model, a single injection of the hydrogel formulation and subsequent sustained release of active ETN efficiently neutralized TNF‐α, resulting in significant suppression of titanium particles‐induced aseptic inflammation and subsequent osteolysis, and the effect was pronouncedly superior to that of an ETN solution.</description><identifier>ISSN: 2642-4150</identifier><identifier>EISSN: 2642-4169</identifier><identifier>DOI: 10.1002/pol.20220337</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Aqueous solutions ; aseptic loosening ; Copolymers ; Cytokines ; Debris ; Degradation ; etanercept ; Hydrogels ; in vivo degradation ; injectable hydrogel ; osteolysis ; Phase transitions ; Polyethylene glycol ; Sol-gel processes ; sustained drug release ; Sustained release ; Transition temperature ; Tumor necrosis factor-TNF ; Wear particles</subject><ispartof>Journal of polymer science (2020), 2022-10, Vol.60 (20), p.2875-2888</ispartof><rights>2022 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3076-4dbf95cd27305955ac49d940e902a9caa38d74a7f566280fb52975e083b51b143</citedby><cites>FETCH-LOGICAL-c3076-4dbf95cd27305955ac49d940e902a9caa38d74a7f566280fb52975e083b51b143</cites><orcidid>0000-0001-7660-3367</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpol.20220337$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpol.20220337$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids></links><search><creatorcontrib>Lei, Kewen</creatorcontrib><creatorcontrib>Wang, Yang</creatorcontrib><creatorcontrib>Peng, Xiaochun</creatorcontrib><creatorcontrib>Yu, Lin</creatorcontrib><creatorcontrib>Ding, Jiandong</creatorcontrib><title>Long‐term delivery of etanercept mediated via a thermosensitive hydrogel for efficient inhibition of wear debris‐induced inflammatory osteolysis</title><title>Journal of polymer science (2020)</title><description>Periprosthetic wear debris‐induced aseptic loosening brings great pain to patients undergoing total joint arthroplasty. Tumor necrosis factor α (TNF‐α) is a pivotal cytokine involved in wear debris‐induced aseptic inflammation and subsequent osteolysis. Herein, we developed an injectable hydrogel system containing etanercept (ETN), a TNF‐α antagonist, to inhibit wear debris‐induced osteolysis. A set of thermosensitive poly(lactide‐co‐glycolide)‐b‐poly(ethylene glycol)‐b‐poly(lactide‐co‐glycolide) (PLGA–PEG–PLGA) copolymers with comparable molecular weights but different LA/GA molar ratios were synthesized by us, and their aqueous solutions presented sol‐to‐gel transitions along with the elevation of temperature. The LA/GA ratio not only impacted the phase transition temperature but also controlled the degradation rate of gel in vivo. The hydrogel with an appropriate in vivo degradation rate was employed to load and deliver ETN, and the drug introduction did not influence on its thermo‐induced gelation behavior. The loaded ETN was released from the gel depot in vitro in a sustained manner for up to 30 days. In a mouse bone‐implanted air pouch model, a single injection of the hydrogel formulation and subsequent sustained release of active ETN efficiently neutralized TNF‐α, resulting in significant suppression of titanium particles‐induced aseptic inflammation and subsequent osteolysis, and the effect was pronouncedly superior to that of an ETN solution.</description><subject>Aqueous solutions</subject><subject>aseptic loosening</subject><subject>Copolymers</subject><subject>Cytokines</subject><subject>Debris</subject><subject>Degradation</subject><subject>etanercept</subject><subject>Hydrogels</subject><subject>in vivo degradation</subject><subject>injectable hydrogel</subject><subject>osteolysis</subject><subject>Phase transitions</subject><subject>Polyethylene glycol</subject><subject>Sol-gel processes</subject><subject>sustained drug release</subject><subject>Sustained release</subject><subject>Transition temperature</subject><subject>Tumor necrosis factor-TNF</subject><subject>Wear particles</subject><issn>2642-4150</issn><issn>2642-4169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp90LtOwzAUBuAIgUQF3XgAS6y0OL7kMlYVNylSGWCOnPi4dZXYxXZbZeMRGHhCngRXBUamc4ZP_y_9SXKV4mmKMbnd2G5KMCGY0vwkGZGMkQlLs_L07-f4PBl7v8aRU54xnI2Sz8qa5df7RwDXIwmd3oEbkFUIgjDgWtgE1IPUIoBEOy2QQGEVrfVgvA6Ro9UgnV1Ch5R1CJTSrQYTkDYr3URhzSFuD8LF_MZpH9u0kds2BmqjOtH3IthDqQ9gu8Frf5mcKdF5GP_ci-T1_u5l_jipFg9P81k1aSnOswmTjSp5K0lOMS85Fy0rZckwlJiIshWCFjJnIlc8y0iBVcNJmXPABW142qSMXiTXx9yNs29b8KFe260zsbImOeEpLwp2UDdH1TrrvQNVb5zuhRvqFNeH6es4ff07feT0yPe6g-FfWz8vqhnFjGf0G75ii3M</recordid><startdate>20221015</startdate><enddate>20221015</enddate><creator>Lei, Kewen</creator><creator>Wang, Yang</creator><creator>Peng, Xiaochun</creator><creator>Yu, Lin</creator><creator>Ding, Jiandong</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><orcidid>https://orcid.org/0000-0001-7660-3367</orcidid></search><sort><creationdate>20221015</creationdate><title>Long‐term delivery of etanercept mediated via a thermosensitive hydrogel for efficient inhibition of wear debris‐induced inflammatory osteolysis</title><author>Lei, Kewen ; Wang, Yang ; Peng, Xiaochun ; Yu, Lin ; Ding, Jiandong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3076-4dbf95cd27305955ac49d940e902a9caa38d74a7f566280fb52975e083b51b143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Aqueous solutions</topic><topic>aseptic loosening</topic><topic>Copolymers</topic><topic>Cytokines</topic><topic>Debris</topic><topic>Degradation</topic><topic>etanercept</topic><topic>Hydrogels</topic><topic>in vivo degradation</topic><topic>injectable hydrogel</topic><topic>osteolysis</topic><topic>Phase transitions</topic><topic>Polyethylene glycol</topic><topic>Sol-gel processes</topic><topic>sustained drug release</topic><topic>Sustained release</topic><topic>Transition temperature</topic><topic>Tumor necrosis factor-TNF</topic><topic>Wear particles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lei, Kewen</creatorcontrib><creatorcontrib>Wang, Yang</creatorcontrib><creatorcontrib>Peng, Xiaochun</creatorcontrib><creatorcontrib>Yu, Lin</creatorcontrib><creatorcontrib>Ding, Jiandong</creatorcontrib><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Journal of polymer science (2020)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lei, Kewen</au><au>Wang, Yang</au><au>Peng, Xiaochun</au><au>Yu, Lin</au><au>Ding, Jiandong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long‐term delivery of etanercept mediated via a thermosensitive hydrogel for efficient inhibition of wear debris‐induced inflammatory osteolysis</atitle><jtitle>Journal of polymer science (2020)</jtitle><date>2022-10-15</date><risdate>2022</risdate><volume>60</volume><issue>20</issue><spage>2875</spage><epage>2888</epage><pages>2875-2888</pages><issn>2642-4150</issn><eissn>2642-4169</eissn><abstract>Periprosthetic wear debris‐induced aseptic loosening brings great pain to patients undergoing total joint arthroplasty. Tumor necrosis factor α (TNF‐α) is a pivotal cytokine involved in wear debris‐induced aseptic inflammation and subsequent osteolysis. Herein, we developed an injectable hydrogel system containing etanercept (ETN), a TNF‐α antagonist, to inhibit wear debris‐induced osteolysis. A set of thermosensitive poly(lactide‐co‐glycolide)‐b‐poly(ethylene glycol)‐b‐poly(lactide‐co‐glycolide) (PLGA–PEG–PLGA) copolymers with comparable molecular weights but different LA/GA molar ratios were synthesized by us, and their aqueous solutions presented sol‐to‐gel transitions along with the elevation of temperature. The LA/GA ratio not only impacted the phase transition temperature but also controlled the degradation rate of gel in vivo. The hydrogel with an appropriate in vivo degradation rate was employed to load and deliver ETN, and the drug introduction did not influence on its thermo‐induced gelation behavior. The loaded ETN was released from the gel depot in vitro in a sustained manner for up to 30 days. In a mouse bone‐implanted air pouch model, a single injection of the hydrogel formulation and subsequent sustained release of active ETN efficiently neutralized TNF‐α, resulting in significant suppression of titanium particles‐induced aseptic inflammation and subsequent osteolysis, and the effect was pronouncedly superior to that of an ETN solution.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><doi>10.1002/pol.20220337</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-7660-3367</orcidid></addata></record> |
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subjects | Aqueous solutions aseptic loosening Copolymers Cytokines Debris Degradation etanercept Hydrogels in vivo degradation injectable hydrogel osteolysis Phase transitions Polyethylene glycol Sol-gel processes sustained drug release Sustained release Transition temperature Tumor necrosis factor-TNF Wear particles |
title | Long‐term delivery of etanercept mediated via a thermosensitive hydrogel for efficient inhibition of wear debris‐induced inflammatory osteolysis |
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