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.

Basic information

Original name

Dexamethasone nanomedicines with optimized drug release kinetics tailored for treatment of site-specific rheumatic musculoskeletal diseases

Authors

LIBÁNSKÁ, Alena, Eva RANDÁROVÁ, Daniela RUBANOVÁ (203 Czech Republic, belonging to the institution), Svitlana SKOROPLYAS, Josef BRYJA (203 Czech Republic, belonging to the institution), Lukáš KUBALA (203 Czech Republic, belonging to the institution), Rafal KONEFAL, Adéla NAVRÁTILOVÁ, Lucie A. CEREZO, Ladislav ŠENOLT and Tomáš ETRYCH

Edition

International Journal of Pharmaceutics, Elsevier B.V. 2024, 0378-5173

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30226 Rheumatology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.800 in 2022

Organization unit

Faculty of Science

DOI

UT WoS

001209747500001

Keywords in English

Controlled drug release; Polymer conjugates; HPMA; Dexamethasone; Hydrazone bond

Tags

Tags

International impact, Reviewed
Změněno: 14/6/2024 11:06, Mgr. Marie Šípková, DiS.

Abstract

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.