Zwitterionic polymer-dexamethasone conjugates penetrate and protect cartilage from inflammation
Improving the pharmacokinetics of intra-articularly injected therapeutics is a major challenge in treating joint disease. Small molecules and biologics are often cleared from the joint within hours, which greatly reduces their therapeutic efficacy. Furthermore, they are often injected at high doses,...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-06-01
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| Series: | Materials Today Bio |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S259000642400108X |
| _version_ | 1797205956575100928 |
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| author | Patrick Weber Maryam Asadikorayem František Surman Marcy Zenobi-Wong |
| author_facet | Patrick Weber Maryam Asadikorayem František Surman Marcy Zenobi-Wong |
| author_sort | Patrick Weber |
| collection | DOAJ |
| description | Improving the pharmacokinetics of intra-articularly injected therapeutics is a major challenge in treating joint disease. Small molecules and biologics are often cleared from the joint within hours, which greatly reduces their therapeutic efficacy. Furthermore, they are often injected at high doses, which can lead to local cytotoxicity and systemic side effects. In this study, we present modular polymer-drug conjugates of zwitterionic poly(carboxybetaine acrylamide) (pCBAA) and the anti-inflammatory glucocorticoid dexamethasone (DEX) to create cartilage-targeted carriers with slow-release kinetics. pCBAA polymers showed excellent cartilage penetration (full thickness in 1 h) and retention (>50 % after 2 weeks of washing). DEX was loaded onto the pCBAA polymer by employing two different DEX-bearing comonomers to produce pCBAA-co-DEX conjugates with different release kinetics. The slow-releasing conjugate showed zero-order release kinetics in PBS over 70 days. The conjugates elicited no oxidative stress on chondrocytes compared to dose-matched free DEX and protected bovine cartilage explants from the inflammatory response after treatment with IL-1β. By combining cartilage targeting and sustained drug release properties, the pCBAA-co-DEX conjugates solve many issues of today's intra-articular therapeutics, which could ultimately enable better long-term clinical outcomes with fewer side effects. |
| first_indexed | 2024-04-24T08:59:22Z |
| format | Article |
| id | doaj.art-206924424462481da1068e33852525d3 |
| institution | Directory Open Access Journal |
| issn | 2590-0064 |
| language | English |
| last_indexed | 2024-04-24T08:59:22Z |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj.art-206924424462481da1068e33852525d32024-04-16T04:09:49ZengElsevierMaterials Today Bio2590-00642024-06-0126101049Zwitterionic polymer-dexamethasone conjugates penetrate and protect cartilage from inflammationPatrick Weber0Maryam Asadikorayem1František Surman2Marcy Zenobi-Wong3Tissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH Zürich, Otto-Stern-Weg 7, 8093, Zürich, SwitzerlandTissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH Zürich, Otto-Stern-Weg 7, 8093, Zürich, SwitzerlandTissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH Zürich, Otto-Stern-Weg 7, 8093, Zürich, SwitzerlandCorresponding author.; Tissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH Zürich, Otto-Stern-Weg 7, 8093, Zürich, SwitzerlandImproving the pharmacokinetics of intra-articularly injected therapeutics is a major challenge in treating joint disease. Small molecules and biologics are often cleared from the joint within hours, which greatly reduces their therapeutic efficacy. Furthermore, they are often injected at high doses, which can lead to local cytotoxicity and systemic side effects. In this study, we present modular polymer-drug conjugates of zwitterionic poly(carboxybetaine acrylamide) (pCBAA) and the anti-inflammatory glucocorticoid dexamethasone (DEX) to create cartilage-targeted carriers with slow-release kinetics. pCBAA polymers showed excellent cartilage penetration (full thickness in 1 h) and retention (>50 % after 2 weeks of washing). DEX was loaded onto the pCBAA polymer by employing two different DEX-bearing comonomers to produce pCBAA-co-DEX conjugates with different release kinetics. The slow-releasing conjugate showed zero-order release kinetics in PBS over 70 days. The conjugates elicited no oxidative stress on chondrocytes compared to dose-matched free DEX and protected bovine cartilage explants from the inflammatory response after treatment with IL-1β. By combining cartilage targeting and sustained drug release properties, the pCBAA-co-DEX conjugates solve many issues of today's intra-articular therapeutics, which could ultimately enable better long-term clinical outcomes with fewer side effects.http://www.sciencedirect.com/science/article/pii/S259000642400108XZwitterionicDexamethasonePolymer-drug conjugateCartilageSustained release |
| spellingShingle | Patrick Weber Maryam Asadikorayem František Surman Marcy Zenobi-Wong Zwitterionic polymer-dexamethasone conjugates penetrate and protect cartilage from inflammation Materials Today Bio Zwitterionic Dexamethasone Polymer-drug conjugate Cartilage Sustained release |
| title | Zwitterionic polymer-dexamethasone conjugates penetrate and protect cartilage from inflammation |
| title_full | Zwitterionic polymer-dexamethasone conjugates penetrate and protect cartilage from inflammation |
| title_fullStr | Zwitterionic polymer-dexamethasone conjugates penetrate and protect cartilage from inflammation |
| title_full_unstemmed | Zwitterionic polymer-dexamethasone conjugates penetrate and protect cartilage from inflammation |
| title_short | Zwitterionic polymer-dexamethasone conjugates penetrate and protect cartilage from inflammation |
| title_sort | zwitterionic polymer dexamethasone conjugates penetrate and protect cartilage from inflammation |
| topic | Zwitterionic Dexamethasone Polymer-drug conjugate Cartilage Sustained release |
| url | http://www.sciencedirect.com/science/article/pii/S259000642400108X |
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