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Targeted therapy of rheumatoid arthritis via macrophage repolarization
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Journal Article
Targeted therapy of rheumatoid arthritis via macrophage repolarization
2021
Overview
The polarization of macrophages plays a critical role in the physiological and pathological progression of rheumatoid arthritis (RA). Activated M1 macrophages overexpress folate receptors in arthritic joints. Hence, we developed folic acid (FA)-modified liposomes (FA-Lips) to encapsulate triptolide (TP) (FA-Lips/TP) for the targeted therapy of RA. FA-Lips exhibited significantly higher internalization efficiency in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells than liposomes (Lips) in the absence of folate. Next, an adjuvant-induced arthritis (AIA) rat model was established to explore the biodistribution profiles of FA-Lips which showed markedly selective accumulation in inflammatory paws. Moreover, FA-Lips/TP exhibited greatly improved therapeutic efficacy and low toxicity in AIA rats by targeting M1 macrophages and repolarizing macrophages from M1 to M2 subtypes. Overall, a safe FA-modified liposomal delivery system encapsulating TP was shown to achieve inflammation-targeted therapy against RA via macrophage repolarization.
Publisher
Taylor & Francis,Taylor & Francis Ltd,Taylor & Francis Group
Subject
/ Animals
/ Arthritis, Experimental - drug therapy
/ Arthritis, Rheumatoid - pathology
/ Diterpenes - administration & dosage
/ Diterpenes - adverse effects
/ Diterpenes - therapeutic use
/ Epoxy Compounds - administration & dosage
/ Epoxy Compounds - adverse effects
/ Epoxy Compounds - pharmacology
/ Epoxy Compounds - therapeutic use
/ Ethics
/ Folic Acid - administration & dosage
/ Folic Acid - adverse effects
/ Folic Acid - therapeutic use
/ Inflammation Mediators - metabolism
/ Lipopolysaccharides - pharmacology
/ Male
/ Mice
/ Nonsteroidal anti-inflammatory drugs
/ Pharmacy
/ Phenanthrenes - administration & dosage
/ Phenanthrenes - adverse effects
/ Phenanthrenes - pharmacology
/ Phenanthrenes - therapeutic use
/ Rats
