Carrier-free poly(glycyrrhetinic acid)-facilitated celastrol-loaded nanoparticle for high-efficiency low-toxicity treatment of rheumatoid arthritis

被引：1

作者：

Zhang, Wenjing ^{[1
]}

Huang, Yuan ^{[1
]}

Li, Jing ^{[1
]}

Zhou, Mei ^{[1
]}

Huang, Weijun ^{[1
]}

Sun, Li ^{[1
,2
,5
]}

Gui, Shuangying ^{[1
,2
,3
,4
,5
]}

Li, Zhenbao ^{[1
,2
,3
,4
,5
]}

机构：

[1] Anhui Univ Chinese Med, Coll Pharm, Hefei 230012, Peoples R China

[2] Anhui Acad Chinese Med, Inst Pharmaceut, Hefei 230012, Peoples R China

[3] Anhui Prov Key Lab Pharmaceut Preparat Technol & A, Hefei 230012, Peoples R China

[4] Engn Technol Res Ctr Modern Pharmaceut Preparat, Hefei 230012, Anhui Province, Peoples R China

[5] Anhui Prov Key Lab Applicat & Transformat Tradit C, Hefei, Peoples R China

来源：

MATERIALS & DESIGN | 2024年 / 241卷

关键词：

Celastrol; Glycyrrhetinic acid; Drug-backboned polyprodrug; High-efficiency low-toxicity; Rheumatoid arthritis; DELIVERY;

D O I：

10.1016/j.matdes.2024.112951

中图分类号：

T [工业技术];

学科分类号：

08 ;

摘要：

Rheumatoid arthritis (RA) is a complex autoimmune disease associated with synovial inflammation and articular cartilage destruction. Currently, high -efficiency low -toxicity management of this intractable disease is highly urgent. Here, a drug-backboned polymer, polyglycyrrhetinic acid (PGA), was synthesized through the condensation of GA, a principal anti-inflammatory component of Glycyrrhiza glabra . PGA was then used as a therapeutic polyprodrug carrier to fabricate carrier -free PGA@Cel nanoparticles (NPs) for treating rheumatoid arthritis. The as -prepared NPs exhibited a uniformly spherical morphology with an average particle size of approximately 180 nm and a celastrol (Cel) loading capacity of around 4.5 %. Upon intravenous injection, the NPs demonstrated prolonged blood circulation, efficient accumulation at inflammatory joints through extravasation via leaky vasculature and subsequent inflammatory cell -mediated sequestration (ELVIS) effect. The present study demonstrated enhanced anti-inflammatory and rheumatic decay efficiency in rat models of antigen -induced arthritis, while simultaneously minimizing off -target toxicity. Overall, our results elucidate that this carrierfree drug-backboned nanopolydrug platform provides a promising strategy for RA therapy.

引用

页数：14