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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F24%3A00584617" target="_blank" >RIV/68081707:_____/24:00584617 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61389013:_____/24:00584617 RIV/00216224:14310/24:00136246 RIV/00216208:11110/24:10482282 RIV/00023728:_____/24:N0000029

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0378517324002138?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0378517324002138?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ijpharm.2024.123979" target="_blank" >10.1016/j.ijpharm.2024.123979</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/NU20-08-00255" target="_blank" >NU20-08-00255: Cílená polymerní terapeutika pro pokročilou léčbu místně specifických revmatických onemocnění pohybového aparátu</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

International Journal of Pharmaceutics

ISSN

0378-5173

e-ISSN

1873-3476

Svazek periodika

654

Číslo periodika v rámci svazku

10 April

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

10

Strana od-do

123979

Kód UT WoS článku

001209747500001

EID výsledku v databázi Scopus

2-s2.0-85187332231