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Folate-modified triptolide liposomes target activated macrophages for safe rheumatoid arthritis therapy

發布時間:1668151053 人氣: 來源:

期刊名:Biomaterials Science

發表日期: 08 Dec 2021

DOI: 10.1039/D1BM01520F

文章地址:https://pubmed.ncbi.nlm.nih.gov/34904598/


ABSTRACT

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial joint hyperplasia, joint inflammation, cartilage erosion and bone destruction. Macrophages play an essential role in the pathogenesis of RA, and folate receptor β (FR-β) is highly expressed on the surface of activated synovial macrophages in RA patients. Triptolide (TP) has anti-inflammatory properties, and it can protect the cartilage matrix, but its clinical application has been limited due to poor solubility, low bioavailability and systemic toxicity. Therefore, we constructed folate-modified triptolide liposomes (FA-TP-Lips) to target macrophages, thereby treating RA in a safe and effective way. The experiments indicated that FA-TP-Lips had properties of small particle size, uniform particle size distribution, high drug encapsulation and long circulation. Furthermore, FA-TP-Lips showed reduced cytotoxicity, increased cellular uptake and significant anti-inflammatory effects in vitro. It also inhibited osteoclastogenesis. In vivo experiments revealed that liposomes could prolong the circulation of TP in the body, as well as exhibit significant cartilage-protective and anti-inflammatory effects with lower toxicity compared with the free TP group, thereby providing a promising new approach for the treatment of RA.


TP was obtained from Pufei De Biotech Co. ltd Chenadu.chinal. Cholesterol and eaa phosphatioycholne EPC wereobtained from Avanti Poar lipidsnc. (Alabaster , ALUSA,DSPE-PEG20 


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