Targeted delivery of celastrol to glomerular endothelium and podocytes for chronic kidney disease treatment  

作　　者：Qingsi Wu Jiading Wang Yuanfang Wang Ling Xiang Yulu Tan Jiaxing Feng Zhirong Zhang Ling Zhang 

机构地区：[1]Key Laboratory of Drug Targeting and Drug Delivery Systems,Ministry of Education,West China School of Pharmacy,No.17,Block 3,Southern Renmin Road,Chengdu 610041,China [2]College of Polymer Science and Engineering,Sichuan University,No.24,South Block 1,First Ring Road,Chengdu 610065,China [3]Med-X Center for Materials,Sichuan University,No.14 Section 3 South Renmin Road,Jinjiang District,Chengdu 610000,China

出　　处：《Nano Research》2022年第4期3556-3568,共13页纳米研究（英文版）

基　　金：This work was supported by the Regional Innovation and Development Joint Fund(No.U20A20411);the National Science Fund for Excellent Young Scholars(No.82022070).

摘　　要：The etiology of chronic kidney disease(CKD)is complex and diverse,which could be briefly categorized to glomerular-or tubularoriginated.However,the final outcomes of CKD are mainly glomerular sclerosis,endothelial dysfunction and injury,and chronic inflammation.Thus,targeted delivery of drugs to the glomeruli in order to ameliorate glomerular endothelial damage may help alleviate CKD and help enrich our knowledge.The herb tripterygium wilfordii shows therapeutic effect on kidney disease,and celastrol(CLT)is one of its active ingredients but with strong toxicity.Therefore,based on the unique structure and pathological characteristics of the glomerulus,we designed a targeted delivery system named peptides coupled CLT-phospholipid lipid nanoparticles(PC-PLNs)to efficiently deliver CLT to damaged endothelial cells and podocytes in the glomerulus for CKD treatment and research.PC-PLNs could effectively inhibit inflammation,reduce endothelial damage,alleviate CKD severity,and reduce the toxicity of CLT.We also studied the mechanism of CLT in the treatment of nephropathy and found that CLT can increase the level of NO by increasing eNOS while inhibiting the expression of VCAM-1,thus provides an anti-inflammatory effect.Therefore,our study not only offered an efficient CKD drug formulation for further development,but also provided new medical knowledge about CKD.

关 键 词：CELASTROL chronic kidney disease(CKD) GLOMERULUS endothelial cells VCAM-1 

分 类 号：R692[医药卫生—泌尿科学]