Effects of nanoparticle‑mediated delivery of pitavastatin on atherosclerotic plaques in ApoE‑knockout mice and THP‑1‑derived macrophages

Abstract

The treatment of atherosclerosis remains complex. Pitavastatin serves an important role in the prevention and treatment of atherosclerosis. The present study aimed to investigate the effects of nanoparticle (NP)-mediated delivery of pitavastatin into atherosclerotic plaques as a novel treatment method for atherosclerosis. The results of the present study demonstrated that pitavastatin-NP was more effective in attenuating the size of atherosclerotic plaques and enhancing the stability of plaques in vitro compared with pitavastatin alone. In an apolipoprotein E (ApoE)-knockout mouse model of atherosclerosis, a single intravenous injection of fluorescein isothiocyanate-NP resulted in the delivery of NP into atherosclerotic plaques for up to 7 days post-injection. In ApoE-knockout mice and THP-1-derived macrophages, pitavastatin-NP attenuated the development of atherosclerosis, which was associated with regulating lipid metabolism, and inhibited the secretion of inflammatory markers compared with pitavastatin alone. Additionally, the treatment advantages of pitavastatin-NP were independent of lipid lowering. The results demonstrated that pitavastatin-NP administration was more effective in attenuating the development of atherosclerotic plaques compared with systemic administration of pitavastatin.

Nanoparticle-Mediated Delivery of Pitavastatin to Monocytes/Macrophages Inhibits Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in <i>Apoe</i>^−/− Mice

“…with Pitava-NPs that we provided, which was consistent with our finding 39) . Pitava-NPs significantly reduced macrophage accumulation in non-AAA lesion, but failed to reduce MCP expression significantly because medial SMCs were still MCP-1 positive even after treatments with Pitava-NPs (Fig.…”