pH and ROS Dual-Sensitive Nanocarriers for the Targeted Co-Delivery and On-Demand Sequential Release of Tofacitinib and Glucosamine for Synergistic Rheumatoid Arthritis Treatment.
Small
; 20(24): e2308520, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38169139
ABSTRACT
Rheumatoid arthritis (RA) progression involves multiple cell types, and sequential drug action on target cells is necessary for RA treatment. Nanocarriers are widely used for RA treatment; however, the targeted delivery and on-demand release of multiple drugs remains challenging. Therefore, in this study, a dual-sensitive polymer is developed using chondroitin sulfate (CS) for the co-delivery of the cartilage repair agent, glucosamine (GlcN), and anti-inflammatory drug, tofacitinib (Tof). In the joint cavity, acidic pH facilitates the cleavage of GlcN from CS polymer to repair the cartilage damage. Subsequently, macrophage uptake via CS-CD44 binding and intracellular reactive oxygen species (ROS) mediate conversion of (methylsulfanyl)propylamine to a hydrophilic segment jointly triggered rapid Tof/GlcN release via micelle disassembly. The combined effects of Tof, GlcN, and ROS depletion promote the M1-to-M2 polarization shift to attenuate inflammation. The synergistic effects of these agents against RA are confirmed in vitro and in vivo. Overall, the dual pH/ROS-sensitive CS nanoplatform simultaneously delivers GlcN and Tof, providing a multifunctional approach for RA treatment with synergistic drug effects.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piperidinas
/
Artritis Reumatoide
/
Pirimidinas
/
Especies Reactivas de Oxígeno
/
Glucosamina
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Small
Asunto de la revista:
ENGENHARIA BIOMEDICA
Año:
2024
Tipo del documento:
Article