Abstract
Cholesterol-rich arterial plaques characterize atherosclerosis, a significant cause of heart disease. Nutraceuticals have received attention over the years, demonstrating potential benefits towards treating and preventing cardiovascular diseases (CVD), including atherosclerosis. Curcumin, a potent polyphenol present in Curcuma longa, has shown remarkable anti-atherosclerotic activity via anti-inflammatory and anti-oxidative properties. The bioavailability and low water solubility of curcumin limit its clinical translational purposes. These issues can be circumvented effectively by nano-drug delivery systems that can target atherosclerotic plaque sites. In this work, we chose to use curcumin and a natural bioenhancer called Bioperine (derived from Piper nigrum) inside a polymeric nano-drug delivery system for targeting atherosclerotic plaque sites. We selected two different ratios of curcumin:Bioperine to study its comparative effect on the inhibition of oxidized low-density lipoprotein (Ox-LDL)-induced foam cell formation. Our studies demonstrated that Cur-Bio PLGA NPs (both ratios) maintained the cell viability in THP-1 monocyte-derived macrophages above 80% at all periods. The 1:0.2:10 ratio of Cur-Bio PLGA NPs at a concentration of 250 μg/mL illustrated an enhanced reduction in the relative cholesterol content in the THP-1-derived foam cells compared to the 1:1:10 ratio. Confocal microscopy analysis also revealed a reduction in macrophage-mediated foam cell formation when administered with both the ratios of Cur-Bio PLGA NPs. Relative fold change in the mRNA expression of the genes involved in the inflammatory pathways in the atherosclerotic process downregulated NF-κB, CCL2/MCP-1, CD-36, and STAT-3 activity while upregulating the SCAR-B1 expression when treated with the Cur-Bio PLGA NPs. This study thus highlights the importance of natural-based compounds towards the therapeutic intervention against atherosclerotic activity when administered as preventive medicine.
Highlights
Based on our optimization studies, we found that from the different ratios of the Cur-Bio PLGA NPs that we developed, NPs of two ratios of curcumin: Bioperine: PLGA (1:1:10 and 1:0.2:10 respectively) displayed monodispersed nanoparticles and high encapsulation efficiencies of the two drugs
As we have already established from our confocal microscopy results that both the ratios of Cur-Bio PLGA NPs (1:1:10 and 1:0.2:10) at 250 μg/mL are effective in inhibiting the Dil-AcLDL uptake by the THP-1 monocyte-derived macrophage cells within 24–48 h, we decided to study the internalization of the Dil-AcLDL by the macrophage cells using flow cytometry analysis
In this study looking at preventing plaque growth, a promising phytonutrients-based nanomedicine, Cur-Bio PLGA NPs, demonstrated anti-atherosclerotic activity by reducing foam cell formation in THP-1 monocyte-derived macrophage cells in an in vitro setting
Summary
Current treatment approaches towards atherosclerosis involve using small-molecule drugs and pro-inflammatory cytokine inhibitors that reduce LDL and cytokine levels, respectively Amidst all such developments, cardiovascular disease remains one of the leading causes of death worldwide, and the potential of such therapies and their direct side effects remains controversial. The appealing nature of nanoparticles in providing selective drug delivery to the cells and tissues while minimizing off-target effects has leverage over the conventional therapies currently in practice for vascular diseases Curcumin delivery via such innovative nanocarriers has been widely studied against cancer therapies and neurodegenerative disorders in the past [20,21,22]. Bioperine delivery via poly-lactic acid (PLA)-chitosanPEG NPs demonstrates the inhibition of P-glycoprotein (P-gp) expression and elevated reactive oxygen species levels to induce cytotoxic effects in multi-drug-resistant breast cancer cells [33]. Since the translation of nutraceuticals via nano-drug delivery systems is the premise of our present work, the co-delivery of curcumin with a natural bio-enhancer such as Bioperine is an exciting approach as a complementary therapy for atherosclerosis, which will add to the growing list of innovative anti-atherosclerotic treatments
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