Tackling Dyslipidemia in Obesity from a Nanotechnology Perspective
Abstract
:1. Introduction
2. Obesity and Its Interrelated Conditions
3. Obesity and Dyslipidemia
4. Current Therapy Approach
5. Nanotechnology and Dyslipidemia in Obesity: An Old Disease with Innovative Treatment Strategies
5.1. Nano-Formulations and/or Drug-Loaded Nanocarrier
5.2. Herbal Nanotherapy
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
References
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Diagnostic Criteria of Dyslipidemia | References |
---|---|
Increased TG and FFA | [23] |
HDL dysfunction | |
Decreased HDL cholesterol | [24] |
Normal or slightly elevated LDL cholesterol or LDL formation | |
Increased VLDL cholesterol or overproduction by liver | [25] |
Apo B concentrations elevated, partially due to hepatic overproduction | [24] |
Low Apo A-I levels | [25] |
Low HDL-levels | [26] |
Decreased circulating TG lipolysis | [24] |
Impaired peripheral FFA uptake | [25] |
Insulin resistance and macrophage infiltration of the adipose tissue, inducing a pro-inflammatory status |
Nanostructure Type | Drug | Observed Effects | References |
---|---|---|---|
Gold nanoparticles (<50 nm) | Adipose homing peptide | Selective targeted delivery on white adipose tissue vasculature in vivo. | [42] |
Prohibitin-targeted nanoparticles with PEG chains (109.2 ± 7.8 nm) | Proapoptotic peptide | Reduces weight gain via the control of the adipose function by 14%. | [43] |
Prohibitin-targeted nanoparticles (around 100 nm) | Cytochrome C | Prevents diet-induced obesity in C57BL/6 mice in a dose-dependent manner; effectively targeted the adipose tissues and the Cytochrome C released at the adipose site from the nanoparticles; caused apoptosis of the adipose cells. | [44] |
Egg-yolk-phosphatidylcholine- and cholesterol-based nanoparticle-conjugated PEG-lipids (around 130 nm) | Prohibitin-targeting peptide | Reduces undesired entrapment in liver and, hence, improves the efficient targeting of adipose vessels. | [45] |
Peptide-ligand-mediated nanocarrier (lipopeptide-modified liposomes of 105.6 ± 13.9 nm) | Linear peptide, followed by an adipose tissue-specific circular peptide (KGGRAKD) | Successful delivery of the aqueous phase to the cytoplasm of primary cultured endothelial cells derived from inguinal adipose tissue. | [46] |
PLGA-b-PEG nanoparticles (about 100 nm) | Endothelial-targeted peptides (iRGD and P3) | Weight gain inhibition was confirmed in the diet-induced obese mouse model. | [47] |
Nano-emulsion based on Capryol PGMC and Cremophor RH40 (139.4 ± 12 nm) | Orlistat | Overcomes high lipophilicity, improves dissolution and pancreatic lipase inhibition in vivo | [48] |
Lipase-sensitive nanocarrier (self-assembled amphiphilic copolymer BTTPFN-g-PCL; 158 nm) | Orlistat | Lowers weight of the liver or fat pads, smaller adipocyte size, and lower total cholesterol level. | [49] |
PLGA-b- PEG-triphenylphosphonium polymer nanoparticles (∼80 to ∼410 nm) | Mitochondrial decoupler 2,4-dinitrophenol | Reduces lipid accumulation in the adipocytes, but may also lead to the excessive generation of reactive oxygen species and its possible impairment in non-adipose tissues. | [50] |
PLGA nanoparticles (177 ± 6 nm) | Dibenzazepine | Browning of adipocytes, consequently improving glucose homeostasis and attenuating body weight gain in the treated diet-induced obese mice. | [51] |
Dextran and dextran-PEG nano-carriers (4–30 nm) | Dexamethasone | Restored the gene expression of key pro-inflammatory cytokines (TNFα, IL-6, MCP-1) and ameliorated many critical effects of obesity-induced inflammation. | [52] |
Polymeric nanoparticles (200 nm) | Rosiglitazone | Alleviated inflammatory reactions in the white adipose tissue and liver. | [53] |
Nanostructure Type | Observed Effects | References |
---|---|---|
Superparamagnetic iron oxide nanoparticles grafted with carboxyethylsilanetriol (very narrow size distribution of <20 nm) | Downregulated the expression of 22 and 29 risk genes and the mRNA expression of lipid and glucose metabolism genes upon exposure to human primary adipocytes. | [56] |
Cerium oxide nanoparticles (5–80 nm) | Reduced the weight gain and lowered the plasma levels of insulin, leptin, glucose, and triglycerides. | [57] |
Chitosan and water-soluble chitosan microparticles and nanoparticles | A significantly lower degree of weight gain in a high-fat-diet rat model, reduced the final amounts of epididymal and perirenal white adipose tissues, liver weight, total serum cholesterol, and low-density lipoprotein cholesterol. | [58] |
Carboxyethylsilanetriol grafted superparamagnetic iron oxide nanoparticles (<10 nm) | Crucial dual role in the expression of 22 and 29 risk genes (based on gene-wide association studies) for obesity and T2DM in human adipocytes. | [56] |
Silica mesoporous particles (2D hexagonal pores) | Decrease in weight and body fat composition without observable toxicological signs or systemic absorption of silica. | [59] |
Gold nanorods energized by an external near-infrared exposure at 800 nm (NanoLipo) | Disruptions in the adipose tissue and removal of 33% subcutaneous tissue and ~60% free fatty acids, leading to a great decrease in the adipose layer thickness at 1 month post-surgery. | [60] |
Hyaluronate gold nanosphere conjugated with photothermal lipolysis | Enables the highly effective photothermal ablation of adipose tissues in C57BL/6 obese mice, successful transdermal delivery, and photothermal lipolysis. | [61] |
Gold nanoparticles (21 nm) | An 8% or 5% reduction in body weight, improved hyperlipidemia, and normal glucose tolerance. | [62] |
Nanostructure Type | Drug | Observed Effects | References |
---|---|---|---|
Nano-selenium | Atorvastatin | Significantly reduced serum TC, TG, and LDL-C contents; declined tissue lesions, such as the aortic arch and liver; enhanced the activities of GPx-1 and SOD in the serum; decreased the MDA content; and increased the SOD activity in rat aorta. | [64] |
Nano-particulate formulation (nano coenzyme Q10 and nano-vitamin E) | Reduction in the number of liver and muscle enzymes and histopathological alterations, together with a marked decline in oxidative stress. | [65] | |
Solid-lipid nanoparticles (glyceryl monostearate, Poloxamer 407; 88.91 + 1.23 nm) | All nano-systems showed increased bioavailability. The nano-sponges were found to be an excellent carrier of the drug, providing a sustained drug release over a prolonged period of time, lowering the LDL, TC, and TG, and increasing the HDL over a period of 7 days. | [66] | |
Nanocrystals (based on didodecyldimethylammonium bromide; 139.6 + 2.21 nm) | |||
Nano-sponges (β-cyclodextrin cross-linked with diphenyl carbonate; 298.2 + 1.02 nm) | |||
Nanostructured lipid carriers (187.6 ± 3.04 nm) | Simvastatin | Enhanced bioavailability and improved biological efficiency of the drug; improved plasma and erythrocyte membrane lipids; maintenance of the erythrocyte oxidant/antioxidant balance; and decreased hemolysis in hyperlipidemic conditions. | [67] |
Solid lipid nanoparticles (palmityl alcohol, Tween 40/Span 40/Myrj 52; ∼130 nm) | Sustained release, significantly reduced the elevated serum lipids, and decreased total cholesterol in hyperlipidemic rats. | [68] | |
Solidified self-nano-emulsifying drug-delivery system (∼100 nm) | Rosuvastatin | Improved drug release (∼95%), reduction in cholesterol, triglyceride, and atherogenic indices, and increased high-density lipoprotein levels. | [69] |
Nanoliposomes (negatively charged surface) | - | Decreased triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, and increased high-density lipoprotein cholesterol in high-cholesterol-diet rabbits. | [70] |
Nanostructure Type | Natural Product | Observed Effects | References |
---|---|---|---|
Gold nanoparticles (20–50 nm with a spherical morphology and crystalline nature) | Salacia chinensis | Decreased the body weight, resistin, liver marker enzymes, leptin, adipose index, and inflammatory markers; increased the levels of high-density lipoprotein, AMP-activated protein kinase, and adiponectin. | [83] |
Gold nanoparticles (hollow spheres of 50–90 nm) | Smilax glabra rhizome | Both anti-obesity and anti-diabetic effects: mediate glucose and insulin discharge; normalize the liver markers, lipid profiles, body weight, body mass index, and hormone profile. | [84] |
Gold nanoparticles (spherical, poly-dispersed, of 20 nm) | Poria cocos | Reduce the weight gain and body mass index, regulate glucose and lipid metabolism, inhibit adipose tissue inflammation, scavenge oxidative stress, and normalize the satiety hormones. | [85] |
Silver nanoparticles (spherical, of 15 nm) | Argyreia nervosa | Inhibitory activity against carbohydrate digestive enzymes α-amylase and α-glucosidase; strong antibacterial activity against foodborne bacteria, Escherichia coli and Staphylococcus aureus. | [86] |
Ligand-coated R-encapsulated nanoparticles (L-Rnano) (spherical shape with a size of 90–110 nm) | Resveratrol | Induced adipose stromal cell differentiation into beige adipocytes, reduced the 40% fat mass and inflammation, and enhanced glucose hemostasis. | [87] |
Poly-vinyl alcohol gelatin nanofibers (200 to 250 nm) | Curcumin | Reduce the number of adipose tissues by up to 4–7% in model rats. | [88] |
Phosphatidylcholine phytosome nanoparticles (51.66–667.24 nm) and phytosome thermogel | Soybean seed extract | Reduction in body weight, adipose tissue weight, and lipid profile. | [89] |
Single-layer nano-emulsion and alginate double-layer nano-emulsion | Oleoresin capsicum | Inhibits intracellular lipid accumulation and triglyceride content and enhances the release of free fatty acids and glycerol into the medium | [90] |
Lipid-derived nano-vesicles (<50 nm and >150 nm) | Citrus sinensis | Increased villi size, reduced triglyceride content, and modulated mRNA levels of TNF-α and IL-1β genes, barrier permeability, fat absorption, and chylomicron release. | [91] |
Gold nanoparticles (size 10–20 nm) | Dendropanax morbifera | Reduced triglyceride content, down-regulated PPAR-γ, CEBPα, Jak2, STAT3, and ap2 expression in 3T3-L1 cells and FAS and acetyl ACC levels in HepG2 cells. | [92] |
Lipid nanocarriers (200 nm) | Capsaicin | Decrease in body weight by up to 15% as compared to the control and improved lipid and glucose profiles. | [93] |
Lipid nanocarriers and liposomes (140 nm and 110) | Resveratrol | Enhanced uncoupling protein 1 and beige marker CD137 expression. | [94] |
Self-assembly and directed assembly of lipid nanocarriers | Silibinin | Prevents liver fibrosis in obese rats, enhanced bioavailability 2.9 fold, and improved therapeutic action. | [95] |
Solid lipid nanoparticles | Hydroxycitric acid | Improved bioavailability, enhanced the pharmacological action, provided a targeted delivery to the adipose tissues, and reduced the associated side effects. | [96] |
Chitosan nanoparticles (210 nm) | Chlorogenic acid | Sustained release property, retained antioxidant activity, and enhanced bioavailability. | [97] |
Cubic phase monoolein nanoparticles (205–295 nm) | Grape, apple, mugwort, barberry root, and green tea extracts | Decreased the blood contents of aspartate aminotransferase, total cholesterol, triglyceride, urea nitrogen, and low-density lipoprotein; promoted the efficacy of the herbal extracts in suppressing body weight gain and liver weight gain in rats. | [98] |
PLGA nanoparticles (Nano-Orz, 214.8 ± 4.3 nm) | γ-Oryzanol | Ameliorated fuel metabolism, with an excellent impact on the dysfunction of the hypothalamus and pancreatic islets; decreased ER stress and inflammation in the liver and adipose tissue. | [99] |
Nanostructure Type | Natural Product | Observed Effects | Reference |
---|---|---|---|
Nano-emulsion with Tween (24.9 ± 1.11 nm) | Garlic oil | Significant effect in lowering the lipid profile and the lipid deposits in hepatic tissues. | [105] |
Gold nanoparticles (smooth spherical morphology with 7–27 nm) | Ziziphus jujube | Significant decrease in the levels of liver, insulin, triglycerides, cholesterol, and total antioxidant capacity. | [106] |
Oil-in-water nano-emulsion (133.4 ± 0.2 nm) | Hibiscus cannabinus L. | Declined accumulation of fat droplets in the liver, lowered cholesterol, decreased number of endogenous antioxidants in the liver, and controlled weight in high-cholesterol-diet-induced rats, with the accelerated renewal of liver cells after injury. | [107] |
Selenium nanoparticles (spherical crystals of 18–50 nm) | Black currant | Increased hypolipidemia antioxidant activity in galactose-treated rats | [108] |
Silver nanoparticles (200 nm) | Nigella Sativa | Decreased levels of triglycerides, cholesterol absorption, low-density lipoproteins, oxidative stress, and increased high-density lipoproteins. | [109] |
Chitosan nanocarrier | Fennel, rosemary volatile oils | Reduced dyslipidemia and CVDs risk, improved liver dysfunction, lowered MDA and TNF-α and blood sugar values. | [110] |
Self-nano-emulsifying delivery system (48% surfactant Kolliphor and 12% co-surfactant PEG 200, 2.8 ± 0.1 nm) | Perillaldehyde-isopropyl myristate/medium chain triglyceride | Hypolipidemic potential: decreased serum TC, TG, and LDL-C while increasing the HDL-C levels. | [111] |
Liposomal nano-formulation (200 nm, spherical and homogenous, with no sign of coalescence) | Perillaldehyde from Perilla frutescens | Decrease in TC, TG, and LDL-C, increase in the HDL-C levels and the activities of SOD and GSH-Px. | [112] |
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Trandafir, L.M.; Dodi, G.; Frasinariu, O.; Luca, A.C.; Butnariu, L.I.; Tarca, E.; Moisa, S.M. Tackling Dyslipidemia in Obesity from a Nanotechnology Perspective. Nutrients 2022, 14, 3774. https://doi.org/10.3390/nu14183774
Trandafir LM, Dodi G, Frasinariu O, Luca AC, Butnariu LI, Tarca E, Moisa SM. Tackling Dyslipidemia in Obesity from a Nanotechnology Perspective. Nutrients. 2022; 14(18):3774. https://doi.org/10.3390/nu14183774
Chicago/Turabian StyleTrandafir, Laura M., Gianina Dodi, Otilia Frasinariu, Alina C. Luca, Lacramioara I. Butnariu, Elena Tarca, and Stefana M. Moisa. 2022. "Tackling Dyslipidemia in Obesity from a Nanotechnology Perspective" Nutrients 14, no. 18: 3774. https://doi.org/10.3390/nu14183774