2024
Dexamethasone nanomedicines with optimized drug release kinetics tailored for treatment of site-specific rheumatic musculoskeletal diseases
LIBÁNSKÁ, Alena, Eva RANDÁROVÁ, Daniela RUBANOVÁ, Svitlana SKOROPLYAS, Josef BRYJA et. al.Základní údaje
Originální název
Dexamethasone nanomedicines with optimized drug release kinetics tailored for treatment of site-specific rheumatic musculoskeletal diseases
Autoři
LIBÁNSKÁ, Alena, Eva RANDÁROVÁ, Daniela RUBANOVÁ (203 Česká republika, domácí), Svitlana SKOROPLYAS, Josef BRYJA (203 Česká republika, domácí), Lukáš KUBALA (203 Česká republika, domácí), Rafal KONEFAL, Adéla NAVRÁTILOVÁ, Lucie A. CEREZO, Ladislav ŠENOLT a Tomáš ETRYCH
Vydání
International Journal of Pharmaceutics, Elsevier B.V. 2024, 0378-5173
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30226 Rheumatology
Stát vydavatele
Nizozemské království
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 5.800 v roce 2022
Organizační jednotka
Přírodovědecká fakulta
UT WoS
001209747500001
Klíčová slova anglicky
Controlled drug release; Polymer conjugates; HPMA; Dexamethasone; Hydrazone bond
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 14. 6. 2024 11:06, Mgr. Marie Šípková, DiS.
Anotace
V originále
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.