<p>Nano-Encapsulation of Coenzyme Q10 in Secondary and Tertiary Nano-Emulsions for Enhanced Cardioprotection and Hepatoprotection in Human Cardiomyocytes and Hepatocytes During Exposure to Anthracyclines and Trastuzumab</p>

Abstract

Introduction CoenzymeQ 10 (CoQ 10 ) is a well-known antioxidant and anti-inflammatory agent with cardioprotective properties. However, clinical trials based on its oral administration have failed to provide significant effect on cardiac functionality. The main limitation of CoQ 10 is based on its very low oral bioavailability and instability that limit dramatically its effects as a cardioprotective agent. Herein, we loaded CoQ 10 in high bioavailable nano-emulsions (NEs) coated with chitosan or chitosan and hyaluronic acid in order to improve its performance. Methods We tested cardioprotective and hepatoprotective effects of CoQ 10 -loaded nano-carriers against Doxorubicin and Trastuzumab toxicities in cardiomyocytes and liver cells through analysis of cell viability, lipid peroxidation, expression of leukotrienes, p65/NF-kB and pro-inflammatory cytokines involved in anticancer-induced cardio and hepatotoxicity. Results Nano-carriers showed high stability and loading ability and increased cell viability both in hepatocytes and cardiomyocytes during anticancer treatments. We observed that these effects are mediated by the inhibition of lipid peroxidation and reduction of the inflammation. CoQ 10 -loaded nano-emulsions showed also strong anti-inflammatory effects reducing leukotriene B4 and p65/NF-κB expression and Interleukin 1β and 6 production during anticancer treatments. Discussion Anthracyclines and Human epidermal growth factor receptor (HER2) inhibitors have shown significant anticancer effects in clinical practice but their use is characterized by cardiotoxicity and hepatotoxicity. Nano-carriers loaded with CoQ 10 showed cardio and hepatoprotective properties mediated by reduction of oxidative damages and pro-inflammatory mediators. These results set the stage for preclinical studies of cardio and hepatoprotection in HER2+ breast cancer-bearing mice treated with Doxorubicin and Trastuzumab.

Cell Membrane-Coated Oil in Water Nano-Emulsions as Biomimetic Nanocarriers for Lipophilic Compounds Conveyance

“…It provides a positively charged surface able to establish an attractive interaction between positive Ct-NEs droplets and negatively charged cell membranes ( Scheme 1 F). The cell membrane shell (371.1 ± 18.71 µg of membrane determined by Bicinchoninic Acid (BCA) assay as reported in Supplementary Materials Figure S3 ) was obtained by adapting a previous procedure [ 20 , 21 , 23 , 24 , 25 , 43 , 44 , 45 , 46 ]. In particular, to obtain a system with the highest degree of monodispersion ( Figure 2 ), a single extrusion cycle was added after the liquid–liquid interface technique, in contrast with the current methodologies [ 47 ].…”

“…Despite the excellent obtained results, it is well-known that perfluorinated compounds are not biodegradable and most of them show a poor solubility in ethanol or acetone, which are the most common solvents used to solubilize/disperse several compounds for therapeutic or diagnostic purposes. By contrast, vegetable oil involved in our O/W NEs, is biocompatible, biodegradable and highly miscible with ethanol and acetone, and so able to encapsulate lipophilic substances such as curcumin [ 5 ], lycopene [ 20 ] and co-enzyme Q10 [ 21 ]. Moreover, our O/W NEs coated by a layer of chitosan (Ct), namely secondary nano-emulsions (SNE), were optimized in terms of formulation and process, in order to provide a shelf life over 1 year [ 22 ] and a consequent exceptional ability to be stably coated with several materials, such as polymers, as well as inorganic materials [ 23 , 24 , 25 ].…”

Nanonutraceuticals: The New Frontier of Supplementary Food

“…The purpose of this work was to protect cardiomyoblast cells from doxorubicin (a strong antineoplastic compound) toxic effects. The proposed nanoemulsions, especially those that were lycopene-loaded, produced an increase in cell viability of 35–40% compared with nanoemulsions only containing doxorubicin, and reduced the release of IL-1β, IL-6, IL-8, nitric oxide, and TNF-α [ 130 ].…”

Cardiotoxicity of Epidermal Growth Factor Receptor 2-Targeted Drugs for Breast Cancer

“…Surprisingly, dietary supplementation of flaxseed (FLX), alpha-linolenic acid (ALA), and secoisolariciresinol diglucoside (SDG) also appeared to have cardioprotective effects ( Asselin et al, 2020 ). Similarly, the incorporation of the antioxidant coenzyme Q (10) into nanoemulsion (NES) reduced the expression of leukotriene B4 and p65/nuclear factor-kappa B (NF-κB) and the production of interleukin-1β and interleukin-6 to protect the heart ( Quagliariello et al, 2020 ).…”