title: Systemic Delivery of Nanoparticles Loaded with Pentagalloyl Glucose Protects Elastic Lamina and Prevents Abdominal Aortic Aneurysm in Rats.
abstract: Degeneration of elastin plays a vital role in the pathology and progression of abdominal aortic aneurysm (AAA). Our previous study showed that pentagalloyl glucose (PGG), a core derivative of tannic acid, hinders the development of AAAs in a clinically relevant animal model when applied locally. In this study, we tested whether targeted nanoparticles (NPs) can deliver PGG to the site of an aneurysm and prevent aneurysmal growth by protecting elastin. PGG-loaded albumin NPs with a surface-conjugated elastin-specific antibody were prepared. Aneurysms were induced by calcium chloride-mediated injury to the abdominal aorta in rats. NPs were injected into the tail vein after 10 days of CaCl2injury. Rats were euthanized after 38 days. PGG delivery led to reduction in macrophage recruitment, matrix metalloproteinase (MMP) activity, elastin degradation, calcification, and development of aortic aneurysm. Such NP delivery offers the potential for the development of effective and safe therapies for AAA.
authors.affiliation: Clemson University, Clemson, SC, USA.
authors.forename: Nasim
authors.initials: N
authors.lastname: Nosoudi
authors.affiliation: Clemson University, Clemson, SC, USA.
authors.forename: Aniqa
authors.initials: A
authors.lastname: Chowdhury
authors.affiliation: Clemson University, Clemson, SC, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Siclari
authors.affiliation: Clemson University, Clemson, SC, USA.
authors.forename: Vaideesh
authors.initials: V
authors.lastname: Parasaram
authors.affiliation: Clemson University, Clemson, SC, USA.
authors.forename: Saketh
authors.initials: S
authors.lastname: Karamched
authors.affiliation: Clemson University, Clemson, SC, USA. narenv@clemson.edu.
authors.forename: Naren
authors.identifier: 0000-0002-4889-6542
authors.initials: N
authors.lastname: Vyavahare
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002122:Calcium Chloride; D002478:Cells, Cultured; D019610:Cytoprotection; D004195:Disease Models, Animal; D004339:Drug Compounding; D065546:Drug Liberation; D004547:Elastic Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004549:Elastin / Q000276:immunology / Q000378:metabolism; D047348:Hydrolyzable Tannins / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D007275:Injections, Intravenous; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D053758:Nanoparticles; D010316:Particle Size; D059748:Proteolysis; D017207:Rats, Sprague-Dawley; D012995:Solubility; D061205:Vascular Calcification / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control
chemical_list: D000906:Antibodies; D047348:Hydrolyzable Tannins; C435084:pentagalloylglucose; D004549:Elastin; D020782:Matrix Metalloproteinases; D002122:Calcium Chloride
keywords: Elastin stabilization and regeneration; Matrix metalloproteinase inhibition