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Systemic Delivery of Nanoparticles Loaded with Pentagalloyl Glucose Protects Elastic Lamina and Prevents Abdominal Aortic Aneurysm in Rats

  • Nasim Nosoudi
  • Aniqa Chowdhury
  • Steven Siclari
  • Vaideesh Parasaram
  • Saketh Karamched
  • Naren VyavahareEmail author
Original Article

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 CaCl2 injury. 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.

Keywords

Elastin stabilization and regeneration Matrix metalloproteinase inhibition 

Abbreviations

AAA

Abdominal aortic aneurysm

BSA

Bovine serum albumin

DIR

1,1-Dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide

EL-NP-Blank

Elastin antibody-conjugated blank NPs

EL-NP-DIR

Elastin antibody-conjugated and DIR dye-loaded NPs

EL-NP-PGG

Elastin antibody-conjugated and PGG-loaded NPs

LOX

Lysyl oxidase

PGG

Pentagalloyl glucose

MMP

Matrix metalloproteinase

NPs

Nanoparticles

Notes

Compliance with Ethical Standards

Conflict of Interest

Last author has received research grants from NIH and Hunter Endowment at Clemson University. Other authors have no conflict of interest.

Funding

The study is financially supported by NIH grant P20GM103444 and the Hunter Endowment at Clemson University to (NV).

Human and Animal Rights and Informed Consent

This article does not contain any studies with human participants performed by any of the authors. Clemson University Animal Research Committee approves all animal use protocols (AUP) for the experimental models. All animals receive humane care in compliance with NIH Public Law 99-158, November 20, 1985, “Animals in Research,” revised in 2015.

Supplementary material

12265_2016_9709_MOESM1_ESM.docx (542 kb)
ESM 1 (DOCX 541 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Clemson UniversityClemsonUSA

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