Targeted therapy of rheumatoid arthritis via macrophage repolarization. (1st January 2021)

• Record Type: Journal Article
• Authors: Zhou, Xu; Huang, Dandan; Wang, Runkong; Wu, Mingquan; Zhu, Liyang; Peng, Wei; Tu, He; Deng, Xuangeng; Zhu, He; Zhang, Zhong; Wang, Xinming; Cao, Xi
• Is Part Of: Drug delivery. Volume 28:Number 1(2021)
• Page Start: 2447
• Page End: 2459
• Publication Date: 2021-01-01
• Subjects: Rheumatoid arthritis -- macrophage repolarization -- folate receptor -- triptolide -- liposomes; Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.1080/10717544.2021.2000679
• Languages: English
• ISSNs: 1071-7544

Abstract

Abstract: 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.