Targeted therapy of glomerulonephritis via salvianolic acid b-loaded biomimetic hybrid nanovesicles driven by homing

Zhi-xiang Yuan; Qingyong Chen; Hongmei Liu; Rongrui Zhang; Yan Jiang; Lu Han; Shuo Wang; Yu Xiong; Xianzhe Li; Qiang Liu; Wen-jing Yi; Yan Ren; Lili He; Shiwei Tang; Yunzhu Lin

Materials & Design (Aug 2024)

Targeted therapy of glomerulonephritis via salvianolic acid b-loaded biomimetic hybrid nanovesicles driven by homing

Zhi-xiang Yuan,
Qingyong Chen,
Hongmei Liu,
Rongrui Zhang,
Yan Jiang,
Lu Han,
Shuo Wang,
Yu Xiong,
Xianzhe Li,
Qiang Liu,
Wen-jing Yi,
Yan Ren,
Lili He,
Shiwei Tang,
Yunzhu Lin

Affiliations

Zhi-xiang Yuan: Key Laboratory of Research and Application of Ethnic Medicine Processing and Preparation on the Qinghai Tibet Plateau, College of Pharmacy & College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, PR China
Qingyong Chen: Department of Cardiology, West China Hospital, Sichuan University, Chengdu 600713, PR China
Hongmei Liu: Key Laboratory of Research and Application of Ethnic Medicine Processing and Preparation on the Qinghai Tibet Plateau, College of Pharmacy & College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, PR China; Department of Pharmacy, People’s Hospital of Xinjin District, Chengdu, 611430, PR China
Rongrui Zhang: Key Laboratory of Research and Application of Ethnic Medicine Processing and Preparation on the Qinghai Tibet Plateau, College of Pharmacy & College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, PR China
Yan Jiang: Sichuan Institute for Drug Control, Sichuan Testing Center of Medical Devices, Chengdu 611731, PR China
Lu Han: Key Laboratory of Research and Application of Ethnic Medicine Processing and Preparation on the Qinghai Tibet Plateau, College of Pharmacy & College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, PR China
Shuo Wang: Key Laboratory of Research and Application of Ethnic Medicine Processing and Preparation on the Qinghai Tibet Plateau, College of Pharmacy & College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, PR China
Yu Xiong: Key Laboratory of Research and Application of Ethnic Medicine Processing and Preparation on the Qinghai Tibet Plateau, College of Pharmacy & College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, PR China
Xianzhe Li: Key Laboratory of Research and Application of Ethnic Medicine Processing and Preparation on the Qinghai Tibet Plateau, College of Pharmacy & College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, PR China
Qiang Liu: Key Laboratory of Research and Application of Ethnic Medicine Processing and Preparation on the Qinghai Tibet Plateau, College of Pharmacy & College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, PR China
Wen-jing Yi: Key Laboratory of Research and Application of Ethnic Medicine Processing and Preparation on the Qinghai Tibet Plateau, College of Pharmacy & College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, PR China
Yan Ren: Key Laboratory of Research and Application of Ethnic Medicine Processing and Preparation on the Qinghai Tibet Plateau, College of Pharmacy & College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, PR China
Lili He: Key Laboratory of Research and Application of Ethnic Medicine Processing and Preparation on the Qinghai Tibet Plateau, College of Pharmacy & College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, PR China
Shiwei Tang: Department of Pharmacy, People’s Hospital of Xinjin District, Chengdu, 611430, PR China
Yunzhu Lin: Department of Pharmacy, Evidence-based Pharmacy Center, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Chengdu 610041, PR China; Corresponding author.

Journal volume & issue: Vol. 244
p. 113178

Abstract

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Background: Mesangial cell (MC)-mediated immune inflammatory injury is a basic pathological process in glomerulonephritis. However, due to the limited drug accumulation and serious adverse effects, it remains challenging to explore a rational delivery system integrating high efficiency and low toxicity to deliver anti-inflammatory drugs to the glomerular MC region. Results: Salvianolic acid B (SAB)-loaded hybrid membrane biomimetic nanovesicles (SAB@HMVs) were developed by fusing erythrocyte membrane nanovesicles with mesenchymal stem cells biomimetic membrane nanovesicles. SAB@HMVs had a spheroidal structure, low cytotoxicity, particle size of 143.83 ± 1.33 nm and exhibited a high drug loading capacity (7.02 %±0.30 %) along with a good sustained release function. The in vitro anti-inflammatory results revealed that HMVs were effectively taken up by MCs and showed significant anti-inflammatory activity. Furthermore, in vivo pharmacodynamic studies revealed that SAB@HMVs could deliver SAB to kidney tissue and elicit an effective anti-inflammatory response to improve the pathological changes in the glomerular mesangial region, significantly reducing the levels of cytokines and alleviating kidney inflammation. Especially, noteworthy was the observation that SAB@HMVs augmented the renal delivery of SAB, downregulated the gene expression of p38 MAPK and NF-κB, inhibited the levels of MMP9 and TNF-α proteins as well as elevated the level of iκB protein, indicating that the anti-inflammatory mechanism of SAB@HMVs should be based on regulating MAPK and NF-κB signaling pathways. Conclusion: We provided a novel strategy to increase nanovesicles accumulation in MCs with the potential to exert anti-inflammatory regulatory effects in glomerulonephritis. Furthermore, this biomimetic hybrid membrane loaded with pure drugs may offer a functional platform to address multiple clinical needs.

Published in Materials & Design

ISSN: 0264-1275 (Print); 1873-4197 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials
Website: https://www.journals.elsevier.com/materials-and-design

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