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Ruxolitinib-loaded cytokine nanosponge alleviated the cytokine storm and dampened macrophage overactivation for the treatment of hemophagocytic lymphohistiocytosis.
- Source :
-
International Journal of Pharmaceutics . May2024, Vol. 657, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
-
Abstract
- Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome characterized by a positive feedback loop between cytokine storm and macrophages and lymphocytes overactivation, which could serve as a valid therapeutic target for HLH treatment. In this study, the clinically extensively used JAK1/2 inhibitor ruxolitinib was encapsulated into macrophage membrane-coated nanoparticles (M@NP-R) with high drug-loading efficiency for targeted HLH treatment. In vitro and in vivo studies demonstrated that M@NP-R not only efficiently adsorbed extracellular proinflammation cytokines, like IFN-γ and IL-6 to alleviate the cytokine storm, but also effectively dampened macrophage activation and proliferation by intracellular JAK/STAT signaling pathway inhibition. M@NP-R treatment significantly ameliorated the clinical and laboratory manifestations of HLH in mouse models, including trilineage cytopenia, hypercytokinemia, organomegaly, hepatorenal dysfunction, and tissue inflammation. Importantly, M@NP-R significantly enhanced the survival of the lethal HLH mice. Altogether, M@NP-R successfully blocked the positive feedback loop between the cytokine storm and macrophage overactivation by depleting extracellular inflammatory cytokines and inhibiting the intracellular JAK/STAT signaling pathway, both of which worked synergistically in HLH treatment. As ruxolitinib has already been extensively used in clinics with favorable safety, and M@NP is biodegradable and highly biocompatible, M@NP-R has good prospects for clinical translation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03785173
- Volume :
- 657
- Database :
- Academic Search Index
- Journal :
- International Journal of Pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 177458006
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2024.124127