Article ; Online: Targeted Intravenous Nanoparticle Delivery: Role of Flow and Endothelial Glycocalyx Integrity.
Annals of biomedical engineering
2020 Volume 48, Issue 7, Page(s) 1941–1954
Abstract: Therapies for atherosclerotic cardiovascular disease should target early disease stages and specific vascular sites where disease occurs. Endothelial glycocalyx (GCX) degradation compromises endothelial barrier function and increases vascular ... ...
| Abstract | Therapies for atherosclerotic cardiovascular disease should target early disease stages and specific vascular sites where disease occurs. Endothelial glycocalyx (GCX) degradation compromises endothelial barrier function and increases vascular permeability. This initiates pro-atherosclerotic lipids and inflammatory cells to penetrate vessel walls, and at the same time this can be leveraged for targeted drug delivery. In prior cell culture studies, GCX degradation significantly increased endothelial cell uptake of nanoparticle vehicles that are designed for drug delivery, compared to the effects of intact GCX. The present study assessed if the cell culture findings translate to selective nanoparticle uptake in animal vessels. In mice, the left carotid artery (LCA) was partially ligated to disturb blood flow, which induces GCX degradation, endothelial dysfunction, and atherosclerosis. After ligation, the LCA vessel wall exhibited a loss of continuity of the GCX layer on the intima. 10-nm gold nanospheres (GNS) coated with polyethylene glycol (PEG) were delivered intravenously. GCX degradation in the ligated LCA correlated to increased GNS infiltration of the ligated LCA wall. This suggests that GCX dysfunction, which coincides with atherosclerosis, can indeed be targeted for enhanced drug delivery, offering a new approach in cardiovascular disease therapy. |
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| MeSH term(s) | Animals ; Atherosclerosis/drug therapy ; Carotid Arteries/pathology ; Endothelium, Vascular/cytology ; Endothelium, Vascular/pathology ; Glycocalyx/pathology ; Gold ; Human Umbilical Vein Endothelial Cells ; Humans ; Male ; Metal Nanoparticles/administration & dosage ; Mice ; Mice, Inbred C57BL ; Polyethylene Glycols | |||||
| Chemical Substances | Polyethylene Glycols (3WJQ0SDW1A) ; Gold (7440-57-5) | |||||
| Language | English | |||||
| Publishing date | 2020-02-18 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 185984-5 | |||||
| ISSN | 1573-9686 ; 0191-5649 ; 0090-6964 | |||||
| ISSN (online) | 1573-9686 | |||||
| ISSN | 0191-5649 ; 0090-6964 | |||||
| DOI | 10.1007/s10439-020-02474-4 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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