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

The etiology of chronic kidney disease (CKD) is complex and diverse, which could be briefly categorized to glomerular- or tubular-originated. However, the final outcomes of CKD are mainly glomerular sclerosis, endothelial dysfunction and injury, and chronic inflammation. Thus, targeted delivery of d...

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Bibliographic Details
Published in:Nano research 2022-04, Vol.15 (4), p.3556-3568
Main Authors: Wu, Qingsi, Wang, Jiading, Wang, Yuanfang, Xiang, Ling, Tan, Yulu, Feng, Jiaxing, Zhang, Zhirong, Zhang, Ling
Format: Article
Language:English
Subjects:
Atomic/Molecular Structure and Spectra
Biomedicine
Biotechnology
Chemistry and Materials Science
Condensed Matter Physics
Damage
Drug delivery
Endothelial cells
Endothelium
Etiology
Glomerulus
Health services
Inflammation
Kidney diseases
Kidneys
Lipids
Materials Science
Medical treatment
Nanoparticles
Nanotechnology
Nephropathy
Peptides
Phospholipids
Research Article
Sclerosis
Toxicity
Vascular cell adhesion molecule 1
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Summary:The etiology of chronic kidney disease (CKD) is complex and diverse, which could be briefly categorized to glomerular- or tubular-originated. 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.
ISSN:1998-0124
1998-0000
DOI:10.1007/s12274-021-3894-x