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Dexamethasone nanomedicines with optimized drug release kinetics tailored for treatment of site-specific rheumatic musculoskeletal diseases
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SYSNO ASEP 0584617 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Dexamethasone nanomedicines with optimized drug release kinetics tailored for treatment of site-specific rheumatic musculoskeletal diseases Tvůrce(i) Libánská, Alena (UMCH-V) RID, ORCID
Randárová, Eva (UMCH-V) RID
Rubanová, Daniela (BFU-R)
Skoroplyas, Svitlana (BFU-R)
Bryja, Josef (BFU-R)
Kubala, Lukáš (BFU-R) RID, ORCID
Konefal, Rafal (UMCH-V) RID, ORCID
Navrátilová, A. (CZ)
Cerezo, L. A. (CZ)
Šenolt, L. (CZ)
Etrych, Tomáš (UMCH-V) RID, ORCIDČíslo článku 123979 Zdroj.dok. International Journal of Pharmaceutics. - : Elsevier - ISSN 0378-5173
Roč. 654, 10 April (2024)Poč.str. 10 s. Jazyk dok. eng - angličtina Země vyd. NL - Nizozemsko Klíč. slova controlled drug release ; polymer conjugates ; HPMA Vědní obor RIV CD - Makromolekulární chemie Obor OECD Polymer science Vědní obor RIV – spolupráce Biofyzikální ústav - Biochemie CEP NU20-08-00255 GA MZd - Ministerstvo zdravotnictví Způsob publikování Omezený přístup Institucionální podpora UMCH-V - RVO:61389013 ; BFU-R - RVO:68081707 UT WOS 001209747500001 EID SCOPUS 85187332231 DOI 10.1016/j.ijpharm.2024.123979 Anotace The application of polymer-based drug delivery systems is advantageous for improved pharmacokinetics, controlled drug release, and decreased side effects of therapeutics for inflammatory disease. Herein, we describe the synthesis and characterization of linear N-(2-hydroxypropyl)methacrylamide-based polymer conjugates designed for controlled release of the anti-inflammatory drug dexamethasone through pH-sensitive bonds. The tailored release rates were achieved by modifying DEX with four oxo-acids introducing reactive oxo groups to the DEX derivatives. Refinement of reaction conditions yielded four well-defined polymer conjugates with varied release profiles which were more pronounced at the lower pH in cell lysosomes. In vitro evaluations in murine peritoneal macrophages, human synovial fibroblasts, and human peripheral blood mononuclear cells demonstrated that neither drug derivatization nor polymer conjugation affected cytotoxicity or anti-inflammatory properties. Subsequent in vivo tests using a murine arthritis model validated the superior anti-inflammatory efficacy of the prepared DEX-bearing conjugates with lower release rates. These nanomedicines showed much higher therapeutic activity compared to the faster release systems or DEX itself. Pracoviště Ústav makromolekulární chemie Kontakt Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Rok sběru 2025 Elektronická adresa https://www.sciencedirect.com/science/article/pii/S0378517324002138?via%3Dihub
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