期刊
ACTA BIOMATERIALIA
卷 42, 期 -, 页码 316-328出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2016.07.007
关键词
Electrospraying; Poly (lactic-co-glycolic acid); Montelukast; Drug-eluting stents; In-stent restenosis
资金
- NRF-Technion Grant [R-398-001-065-592]
- Department of Mechanical Engineering, NUS, Singapore
Drug-eluting stents (DESs), have shown promising results in prevention of in-stent restenosis after percutaneous coronary intervention (PCI). The elevated level of leukotrienes (LTs) detected in injured arteries after PCI, together with the potential role of LTs in inflammatory cascades and structural alterations in arterial wall provides the rationale for development of therapeutic strategies for prevention of in-stent restenosis using LTs receptor antagonists. Montelulcast (MK) is a selective cysLT(1) receptor antagonist, with anti-inflammatory and anti-proliferative properties, which has been used for treatment of various diseases. Here, we report on the fabrication of MK/PLGA particles by electrospraying, aiming towards the development of particle based coating of DESs. The electrosprayed particles incorporated with 3% and 6% w/w MK exhibited fairly spherical shape with smooth surfaces and narrow size distribution. Sustained release of MK for up to 40 days was obtained for both formulations, with higher initial burst release and drug release rate for the particles with higher drug loading. The LTD4 induced proliferation and migration of human coronary artery smooth muscle cells (HCASMCs) by 35% and 85%, respectively, which was substantially antagonized using MM incorporated particles. Nevertheless, MM antagonism preserved the normal proliferation and migration of human coronary artery endothelial cells (HCAECs). Moreover, MK antagonism inhibited the LTD4 induced phenotypic transition of HCASMCs from contractile to synthetic type. The electrosprayed MK-PLGA particles can be employed as a coating for DESs to inhibit the formation of neointimal hyperplasia responsible for in-stent restenosis, yet preserve the healing rate of the stented vessel. Statement of significant Montelukast (MM) is a selective cysLT(1) receptor antagonist, with anti-inflammatory and anti-proliferative properties. The LTD4 induced proliferation and migration of human coronary artery smooth muscle cells by 35% and 85%, respectively, which was substantially antagonized using MM incorporated particles. MM antagonism preserved the normal proliferation and migration of human coronary artery endothelial cells. The MM antagonism inhibited the phenotypic transition of human coronary artery smooth muscle cells from contractile to synthetic one induced by LTD4. The electrosprayed MK-PLGA particles can be employed as coating for DESs to inhibit formation of neointimal hyperplasia, responsible for in-stent restenosis. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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