title: Therapeutic Efficacy of an ω-3-Fatty Acid-Containing 17-β Estradiol Nano-Delivery System against Experimental Atherosclerosis.
abstract: Atherosclerosis and its consequences remain prevalent clinical challenges throughout the world. Initiation and progression of atherosclerosis involves a complex, dynamic interplay among inflammation, hyperlipidemia, and endothelial dysfunction. A multicomponent treatment approach targeted for delivery within diseased vessels could prove beneficial in treating atherosclerosis. This study was undertaken to evaluate the multimodal effects of a novel ω-3-fatty acid-rich, 17-β-estradiol (17-βE)-loaded, CREKA-peptide-modified nanoemulsion system on experimental atherosclerosis. In vitro treatment of cultured human aortic endothelial cells (ECs) with the 17-βE-loaded, CREKA-peptide-modified nanoemulsion system increased cellular nitrate/nitrite, indicating improved nitric oxide formation. In vivo, systemic administration of this nanoemulsion system to apolipoprotein-E knock out (ApoE-/-) mice fed a high-fat diet significantly improved multiple parameters related to the etiology and development of occlusive atherosclerotic vasculopathy: lesion area, circulating plasma lipid levels, and expression of aortic-wall inflammatory markers. These salutary effects were attributed selectively to the 17-βE and/or ω-3 polyunsaturated fatty acid components of the nano-delivery system. At therapeutic doses, the 17-βE-loaded, CREKA-peptide modified nanoemulsion system appeared to be biocompatible in that it elicited no apparent adverse/toxic effects, as indexed by body weight, plasma alanine aminotransferase/aspartate aminotransferase levels, and liver and kidney histopathology. The study demonstrates the therapeutic potential of a novel, 17-βE-loaded, CREKA-peptide-modified nanoemulsion system against atherosclerosis in a multimodal fashion by reducing lesion size, lowering the levels of circulating plasma lipids and decreasing the gene expression of inflammatory markers associated with the disease.
authors: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts, United States of America.
authors: Dipti
authors: D
authors: Deshpande
authors: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts, United States of America.
authors: Sravani
authors: S
authors: Kethireddy
authors: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts, United States of America.|Center for Drug Discovery, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts, United States of America.
authors: David R
authors: DR
authors: Janero
authors: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts, United States of America.|Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Mansoor M
authors: MM
authors: Amiji
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D015415:Biomarkers; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004655:Emulsions / Q000737:chemistry; D042783:Endothelial Cells / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage* / Q000737:chemistry; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D036103:Nanotechnology; D009569:Nitric Oxide / Q000096:biosynthesis; D009842:Oligopeptides / Q000737:chemistry; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D004655:Emulsions; D015525:Fatty Acids, Omega-3; D008055:Lipids; D009842:Oligopeptides; C542438:cysteinyl-arginyl-glutamyl-lysyl-alanyl; D009569:Nitric Oxide; D004958:Estradiol