Polymeric Aggregate-Embodied Hybrid Nitric-Oxide-Scavenging and Sequential Drug-Releasing Hydrogel for Combinatorial Treatment of Rheumatoid Arthritis
© 2021 Wiley-VCH GmbH.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 33(2021), 34 vom: 08. Aug., Seite e2008793 |
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| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2021
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| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article hydrogels nitric oxide rheumatoid arthritis stimuli-responsive materials Anti-Inflammatory Agents Azides Delayed-Action Preparations Drug Carriers Hydrogels mehr... |
| Zusammenfassung: | © 2021 Wiley-VCH GmbH. Selective depletion of overproduced nitric oxide (NO) with nanoscavengers is a promising approach for treating rheumatoid arthritis (RA), preventing both oxidative/nitrosative stress and the upregulation of immune cells. However, its practical applications are limited owing to the minimum time interval between intra-articular injections and unwanted off-target NO depletion. Herein, the rational design of an injectable in situ polymeric aggregate-embodied hybrid NO-scavenging and sequential drug-releasing (M-NO) gel platform for the combinatorial treatment of RA by incorporating a "clickable" NO-cleavable cross-linker (DA-NOCCL) is reported. This network is held together with polymeric aggregates to achieve a self-healing capability for visco-supplementation and on-demand dual drug (both hydrophilic and hydrophobic)-releasing properties, depending on the NO concentration. Moreover, consecutive NO-scavenging action reduces pro-inflammatory cytokine levels in lipopolysaccharides-stimulated macrophage cell lines in vitro. Finally, the intra-articularly injected M-NO gel with anti-inflammatory dexamethasone significantly alleviates the symptoms of RA, with negligible toxicity, in animal models. It is believed that this novel M-NO gel platform will provide a guideline for the combinatorial treatment of RA and various NO-related diseases |
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| Beschreibung: | Date Completed 18.01.2022 Date Revised 18.01.2022 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202008793 |