Dexamethasone nanomedicines with optimized drug release kinetics tailored for treatment of site-specific rheumatic musculoskeletal diseases
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
38458405
DOI
10.1016/j.ijpharm.2024.123979
PII: S0378-5173(24)00213-8
Knihovny.cz E-zdroje
- Klíčová slova
- Controlled drug release, Dexamethasone, HPMA, Hydrazone bond, Polymer conjugates,
- MeSH
- antiflogistika terapeutické užití MeSH
- dexamethason MeSH
- doxorubicin chemie MeSH
- leukocyty mononukleární * MeSH
- lidé MeSH
- myši MeSH
- nanomedicína MeSH
- nosiče léků chemie MeSH
- polymery chemie MeSH
- revmatické nemoci * MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiflogistika MeSH
- dexamethason MeSH
- doxorubicin MeSH
- nosiče léků MeSH
- polymery MeSH
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.
Institute of Biophysics of the Czech Academy of Sciences Czech Republic
Institute of Macromolecular Chemistry Czech Academy of Sciences Prague Czech Republic
Citace poskytuje Crossref.org