کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
877540 911033 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Engineering of an ω-3 polyunsaturated fatty acid-containing nanoemulsion system for combination C6-ceramide and 17β-estradiol delivery and bioactivity in human vascular endothelial and smooth muscle cells
موضوعات مرتبط
مهندسی و علوم پایه سایر رشته های مهندسی مهندسی پزشکی
پیش نمایش صفحه اول مقاله
Engineering of an ω-3 polyunsaturated fatty acid-containing nanoemulsion system for combination C6-ceramide and 17β-estradiol delivery and bioactivity in human vascular endothelial and smooth muscle cells
چکیده انگلیسی

Delayed endothelial cell (EC) regeneration and the medial vascular smooth muscle cells (VSMCs) proliferation contribute to arterial restenosis. Although ω-3-polyunsaturated fatty acids (PUFAs), 17β-estradiol (17-βE) and C6-ceramide (CER) have shown therapeutic promise in addressing restenosis, extensive protein binding and lipophilicity complicate their (co-)delivery to cellular targets. We report engineering of an ω-3-PUFA-rich oil-in-water nanoemulsion formulation that effectively delivers 17-βE and CER cargo to cultured vascular cells. The cargo-free, ω-3-PUFA-rich nanoemulsion itself typically reduced growth factor-stimulated cellular proliferation, as did nanoemulsion-delivered CER alone, through enhanced pro-apoptotic caspase 3/7 activity. 17-βE loaded nanoemulsion inhibited VSMC proliferation and supported EC proliferation, responses associated with the mitogen-activated-protein-kinase (MAPK) signaling. Co-administration of 17-βE and CER loaded nanoemulsions exerted an anti-proliferative effect more pronounced on VSMCs than ECs. These therapeutically beneficial responses to ω-3-PUFA, CER, and/or 17-βE in our nanoemulsion formulation invite evaluation of this novel approach in animal models of restenosis and other occlusive vasculopathies.From the Clinical EditorThis team of investigators report the engineering of an ω-3-PUFA-rich oil-in-water nanoemulsion formulation that effectively delivers 17-βE and C6-ceramide cargo to cultured vascular cells in an effort to address vascular restenosis. Further preclinical studies will be needed in animal models before this approach could be considered for clinical trials.

Graphical AbstractA novel flax-seed oil (ω-3 polyunsaturated fatty acid) containing oil in water nanoemulsion system was developed to encapsulate and deliver two hydrophobic molecules – C6-ceramide and 17β-estradiol to the vascular cells. With an average droplet size of less than 200 nm, the nanoemulsion system efficiently delivered the drug payload within the lysosomes of the vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) and selectively inhibited the proliferation of the VSMCs. This selectivity towards VSMCs along with its nanosize and ω-3 polyunsaturated fatty acid content may prove beneficial as a multimodal approach for treatment of disorders like restenosis and atherosclerosis.Figure optionsDownload high-quality image (275 K)Download as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nanomedicine: Nanotechnology, Biology and Medicine - Volume 9, Issue 7, October 2013, Pages 885–894
نویسندگان
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