Role of dexamethasone/captopril co-loaded immunoliposome-nanoparticle hybrids on the regulation of macrophage polarization in mice with glomerulonephritis
10.16438/j.0513-4870.2022-0568
- VernacularTitle:载地塞米松/卡托普利免疫纳米微粒调控肾小球肾炎小鼠中巨噬细胞极化的研究
- Author:
Xian-zhe LI
1
;
Liu-ting ZHOU
2
;
Yue ZHAO
3
;
Tian-qing LIU
4
;
Hong-mei LIU
1
;
Li-li HE
1
;
Zhi-xiang YUAN
1
;
Lu HAN
1
,
5
Author Information
1. College of Pharmacy, Southwest Minzu University, Chengdu 610225, China
2. College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611134, China
3. Department of Pharmacy, Sichuan Tianfu New Area People's Hospital, Chengdu 610213, China
4. Queensland Institute of Medical Research, Herston 4006, Australia
5. Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Chengdu 610041, China
- Publication Type:Research Article
- Keywords:
glomerulonephritis;
macrophage polarization;
renal targeting;
examethasone;
captopril
- From:
Acta Pharmaceutica Sinica
2022;57(8):2388-2398
- CountryChina
- Language:Chinese
-
Abstract:
In this study, dexamethasone (DXMS) and captopril (CAP) were co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles with a surface coating of a phospholipid bilayer, and then the core-shell nanoparticles were modified with polyethylene glycol and integrin α8 antibody to obtain immunoliposome-nanoparticle hybrids (DXMS/CAP@PLGA-ILs). The role of nanoparticles on the renal targeting, anti-inflammatory effects, and macrophage differentiation were investigated. The results showed that the particle size of the nanoparticles was 115.9 ± 2.89 nm, and the core-shell structure could be observed under an electron microscope. The drug loading capacity of DXMS and CAP was 5.72% ± 0.37% and 7.51% ± 0.07%, respectively. The results of in vitro experiments showed that DXMS/CAP@PLGA-ILs could reduce the secretion of specific cytokines and the mRNA expression of markers in M2-type macrophages, thus promoting the differentiation of M2-type macrophages in the direction of unpolarized macrophages. In vivo experiments in mice showed that DXMS/CAP@PLGA-ILs had a significant renal targeting effect, which could restore the renal index, serum creatinine, and urea nitrogen levels of mesangial proliferative glomerulonephritis in mice. Moreover, DXMS/CAP@PLGA-ILs could reduce both the secretion of inflammatory cytokines and the mRNA expression levels of M1 and M2 macrophage markers in the kidney. All the animal experiments were in accordance with the regulations of Animal Ethics Committee of Sichuan Agricultural University. In conclusion, renal-targeting DXMS/CAP@PLGA-ILs could effectively regulate the polarization of macrophages and had an "anti-inflammatory/anti-fibrosis" therapeutic effect, providing a new strategy and basis for the targeted therapy of glomerulonephritis.
