Immuno-Nanoparticles Developed Using Dexamethasone and Captopril Co-Loaded PLGA Improve Glomerulonephritis Through Modulating Macrophage Polarization

Abstract

The purpose of this study was to prepare liposome-coated poly(lactic-co-glycolic acid) co-loaded with dexamethasone (DXMS, D) and captopril (CAP, C) loading with PLGA nanoparticles (P) and modified polyethylene glycol and integrin α8 antibody on the surface of nanoparticles to obtain double-drug-loaded core–shell immunoliposome composite nanoparticles (DCPI), and then studied the loading Kidney targeting, anti-inflammatory effects and effects on macrophage differentiation of drug nanoparticles. In vitro cell experiments showed that DCPI could reduce the secretion of M2 macrophage-specific cytokines and the RNA expression levels of markers, and promote M2 macrophages toward unpolarized macrophages differentiation. In vivo experiments showed that DCPI had significant renal targeting, normalized renal index, serum creatinine, and blood urea nitrogen levels in mice with mesangial proliferative glomerulonephritis, and reduced inflammatory cytokines in the kidney’s secretion, and decreased RNA expression of M1 and M2 macrophage markers in kidneys. In conclusion, kidney-targeted DCPI nanoparticles can effectively regulate the polarization of macrophages, play an “anti-inflammatory/anti-fibrotic” therapeutic effect, and be a target for glomerulonephritis. Treatment provides new strategies and evidence.