Atorvastatin (ATV)-Loaded Lipid Bilayer-Coated Mesoporous Silica Nanoparticles Enhance the Therapeutic Efficacy of Acute Kidney Injury

Abstract

Background: Acute kidney injury (AKI) increases the risk of chronic kidney disease. Atorvastatin (ATV)-loaded lipid bilayer-coated mesoporous silica nanoparticles (L-AMSNs) were synthesized, and their physicochemical parameters were characterized. L-AMSNs exhibited excellent stability; it did not increase in size over time, indicating that the lipid membrane coating prohibited mesoporous silica nanoparticles (MSNs) coalescence. Results: The rate of drug release differed significantly between AMSNs and L-AMSNs at all tested time points. A remarkable improvement in hydrogen peroxide (H2O2)-treated human umbilical vein endothelial cell (HUVEC) viability was observed after treatment with L-AMSNs; the malondialdehyde (MDA) level was significantly reduced compared to control cells. The extent of apoptosis was only 15% that of control H2O2-treated cells. L-AMSNs induced a remarkable decrease in the levels of pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6), showing the therapeutic potential of nanocarrier-based ATV. L-AMSNs significantly increased the superoxide dismutase level and decreased the MDA level, indicating superior anti-inflammatory activity under conditions of oxidative stress. The L-AMSN showed a remarkable improvement in the outer stripe of outer medulla (OSOM) region and maintained the tubular structure of the kidney tissue. Besides, kidney injury score of L-AMSN is significantly lower compared to that of LPS-AKI and ATV indicating the excellent therapeutic efficacy of nanoparticulate system based L-AMSN. Conclusions: Nanoparticles system-based L-AMSNs maintained the tubular structure of kidney tissue, indicating excellent therapeutic efficacy. After clinical translation, L-AMSNs could serve as a promising treatment for AKI.