J 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.