Nanoparticle-based targeted delivery of pentagalloyl glucose reverses elastase-induced abdominal aortic aneurysm and restores aorta to the healthy state in mice

• Published in: PloS one 2020-03, Vol.15 (3), p.e0227165
• Main Authors: Dhital, Saphala, Vyavahare, Naren R
• Format: Article
• Language: English
• Subjects: Abdomen; Abdominal aortic aneurysm; Aneurysm; Aneurysms; Animals; Anti-inflammatory agents; Antibodies - administration & dosage; Antibodies - immunology; Aorta; Aorta, Abdominal - diagnostic imaging; Aorta, Abdominal - drug effects; Aorta, Abdominal - pathology; Aortic aneurysm; Aortic Aneurysm, Abdominal - chemically induced; Aortic Aneurysm, Abdominal - diagnostic imaging; Aortic Aneurysm, Abdominal - drug therapy; Aortic aneurysms; Bioengineering; Biology and Life Sciences; Body weight; Coronary vessels; Degeneration; Diameters; Disease Models, Animal; Drug Carriers - chemistry; Drug dosages; Elastase; Elastin; Elastin - antagonists & inhibitors; Elastin - immunology; Engineering and Technology; Ethanol; Extracellular matrix; Extracellular Matrix - drug effects; Extracellular Matrix - pathology; Fluorescent dyes; Fluorescent indicators; Gelatinase A; Gelatinase B; Glucose; Gold; Homeostasis; Humans; Hydrolyzable Tannins - administration & dosage; Immunoconjugates - administration & dosage; Immunoconjugates - immunology; Immunoglobulins; Infiltration; Inflammation; Injections, Intravenous; Macrophages; Male; Matrix metalloproteinase; Matrix metalloproteinases; Medicine and Health Sciences; Metal Nanoparticles - chemistry; Mice; Nanoparticles; Pancreas; Pancreatic elastase; Pancreatic Elastase - administration & dosage; Pancreatic Elastase - toxicity; Polyphenols; Research and Analysis Methods; Serum Albumin, Bovine - chemistry; Smooth muscle; Stabilizers (agents); Strain; Therapy; Ultrasonic imaging; Ultrasonography
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0227165

Abdominal aortic aneurysms (AAA) is a life-threatening weakening and expansion of the abdominal aorta due to inflammatory cell infiltration and gradual degeneration of extracellular matrix (ECM). There are no pharmacological therapies to treat AAA. We tested the hypothesis that nanoparticle (NP) therapy that targets degraded elastin and delivers anti-inflammatory, anti-oxidative, and ECM stabilizing agent, pentagalloyl glucose (PGG) will reverse advance stage aneurysm in an elastase-induced mouse model of AAA. Porcine pancreatic elastase (PPE) was applied periadventitially to the infrarenal aorta in mice and AAA was allowed to develop for 14 days. Nanoparticles loaded with PGG (EL-PGG-NPs) were then delivered via IV route at 14-day and 21-day (10 mg/kg of body weight). A control group of mice received no therapy. The targeting of NPs to the AAA site was confirmed with fluorescent dye marked NPs and gold NPs. Animals were sacrificed at 28-d. We found that targeted PGG therapy reversed the AAA by decreasing matrix metalloproteinases MMP-9 and MMP-2, and the infiltration of macrophages in the medial layer. The increase in diameter of the aorta was reversed to healthy controls. Moreover, PGG treatment restored degraded elastic lamina and increased the circumferential strain of aneurysmal aorta to the healthy levels. Our results support that site-specific delivery of PGG with targeted nanoparticles can be used to treat already developed AAA. Such therapy can reverse inflammatory markers and restore arterial homeostasis.