Synergistic effects of liposomes encapsulating atorvastatin calcium and curcumin and targeting dysfunctional endothelial cells in reducing atherosclerosis

Abstract

BackgroundAtherosclerosis is a major cardiovascular disease that causes ischemia of the heart, brain, or extremities, and can lead to infarction. The hypolipidemic agent atorvastatin calcium (Ato) alleviates atherosclerosis by reducing plasma lipid and inflammatory factors. However, the low bioavailability of Ato limits its widespread use and clinical effectiveness. Curcumin (Cur), a natural polyphenol with antioxidation and anti-inflammation bioactivities, has potential anti-atherosclerosis activity and may reduce Ato-induced cytotoxicity.Materials and methodsLiposomes modified using a targeting ligand (E-selectin-binding peptide) were prepared to co-deliver Ato and Cur to dysfunctional endothelial cells (ECs) overexpressing E-selectin. Molecules involved in the inhibition of adhesion (E-selectin and intercellular cell adhesion molecule-1 [ICAM-1]) and inflammation (IL-6 and monocyte chemotactic protein 1 [MCP-1]) in human aortic endothelial cells were evaluated using real-time quantitative PCR, flow cytometry, and immunofluorescence staining. The antiatherosclerosis effects of liposomes co-loaded with Ato and Cur in vivo were evaluated using ApoE knockout (ApoE−/−) mice.ResultsTargeted liposomes delivered Ato and Cur to dysfunctional ECs, resulting in synergistic suppression of adhesion molecules (E-selectin and ICAM-1) and plasma lipid levels. Moreover, this treatment reduced foam cell formation and the secretion of inflammatory factors (IL-6 and MCP-1) by blocking monocyte migration into the intima. In addition, Cur successfully reduced Ato-inducible cytotoxicity.ConclusionBoth in vitro and in vivo experiments demonstrated that cell-targeted co-delivery of Ato and Cur to dysfunctional ECs drastically reduces atherosclerotic lesions with fewer side effects than either Ato or Cur alone.

Efficacy of Curcumin on Aortic Atherosclerosis: A Systematic Review and Meta-Analysis in Mouse Studies and Insights into Possible Mechanisms

“…Among these, 8 studies [11,[22][23][24][25][26][27] were excluded due to no available outcome data that met our inclusion criteria, and one study [28] was excluded because of the improper participants (not mice). Thus, we included 10 eligible studies [8,9,12,17,18,[29][30][31][32][33] in this systematic review and metaanalysis. Two of the studies [17,18] contained multiple dosages of curcumin and were then considered a total of six independent experiments as we have mentioned in the eligibility criteria.…”

Role of Polyphenols and Carotenoids in Endothelial Dysfunction: An Overview from Classic to Innovative Biomarkers

“…Lately, the synergistic effect of current antihyperglycemic drugs already in use together with natural bioactive compounds has been tested as a complementary therapeutic approach to improve the bioactivities and bioavailability of these compounds in order to treat inflamed ECs and prevent cardiovascular events in diabetic patients [ 190 , 191 ].…”

Harnessing host–virus evolution in antiviral therapy and immunotherapy

“…Since viruses typically infect and replicate best in only a limited set of host tissues, delivering therapies to specific tissues may mitigate adverse effects. Synthetic lipid nanoparticles (LNPs) protect and deliver small RNAs for RNAi‐based therapy as well as synthetic vaccines and bioactive compounds, while modified viruses or virus‐like particles deliver RNA interference (RNAi)‐based therapies as well as nucleases and DNA for gene therapy . Despite additional challenges as outlined below, these technologies are currently applied to deliver specific treatments for viral infection, cardiovascular disease, inherited genetic disorders and cancer immunotherapy in animal models and humans …”