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Nanoparticles for localized delivery of hyaluronan oligomers towards regenerative repair of elastic matrix.

Abstract：

:Abdominal aortic aneurysms (AAAs) are rupture-prone progressive dilations of the infrarenal aorta due to a loss of elastic matrix that lead to weakening of the aortic wall. Therapies to coax biomimetic regenerative repair of the elastic matrix by resident, diseased vascular cells may thus be useful to slow, arrest or regress AAA growth. Hyaluronan oligomers (HA-o) have been shown to induce elastic matrix synthesis by healthy and aneurysmal rat aortic smooth muscle cells (SMCs) in vitro but only via exogenous dosing, which potentially has side-effects and limitations to in vivo delivery towards therapy. In this paper, we describe the development of HA-o loaded poly(lactide-co-glycolide) nanoparticles (NPs) for targeted, controlled and sustained delivery of HA-o towards the elastogenic induction of aneurysmal rat aortic SMCs. These NPs were able to deliver HA-o over an extended period (>30 days) at previously determined elastogenic doses (0.2-20 μg ml(-1)). HA-o released from the NPs led to dose-dependent increases in elastic matrix synthesis, and the recruitment and activity of lysyl oxidase, the enzyme which cross-links elastin precursor molecules into mature fibers/matrix. Therefore, we were able to successfully develop a nanoparticle-based system for controlled and sustained HA-o delivery for the in vitro elastogenic induction of aneurysmal rat aortic smooth muscle cells.

journal_name

Acta Biomater

journal_title

Acta biomaterialia

authors

Sylvester A,Sivaraman B,Deb P,Ramamurthi A

doi

10.1016/j.actbio.2013.07.032

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

9292-302

issue

12

eissn

1742-7061

issn

1878-7568

pii

S1742-7061(13)00380-2

journal_volume

9

pub_type

杂志文章

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