Dual targeted delivery of statins and nucleic acids by chitosan-based nanoparticles for enhanced antiatherosclerotic efficacy

Biomaterials. 2021 Dec 15;280:121324. doi: 10.1016/j.biomaterials.2021.121324. Online ahead of print.ABSTRACTCardiovascular disease caused by atherosclerosis is a leading cause of morbidity and mortality worldwide. Owing to the synergistic regulation of cholesterol metabolism and lesion inflammation, the simultaneous administration of statins and nucleic acids is expected to alleviate atherosclerosis. In this work, we prepared atorvastatin- and galactose-modified trimethyl chitosan nanoparticles (GTANPs) with dual targeting to hepatocytes and lesional macrophages for encapsulating Baf60a siRNA (siBaf60a) and anti-miR-33 pDNA (pAnti-miR-33), attaining the effective codelivery of statins and nucleic acids. We demonstrated that GTANPs/siBaf60a and GTANPs/pAnti-miR-33 had in vitro antiinflammatory and lipid regulating efficacy. In ApoE-knockout atherosclerotic mice, intravenously injected GTANPs/siBaf60a synergistically reduced the plasma cholesterol and atherosclerotic plaque area; more importantly, orally delivered GTANPs/pAnti-miR-33 synergistically increased the levels of plasma high-density lipoprotein cholesterol (HDL-C) and antiinflammatory cytokines, resulting in a satisfactory antiatherosclerotic outcome. Our results suggest that codelivery of statins and nucleic acids provides a promising strategy for the treatment of atherosclerosis.PMID:34933253 | DOI:10.1016/j.biomaterials.2021.121324

Source: Biomaterials - December 21, 2021 Category: Materials Science Authors: Ting Jiang Lu Xu Mengxin Zhao Fei Kong Xinrong Lu Cui Tang Chunhua Yin Source Type: research