Open AccessTargeted Intravenous Nanoparticle Delivery: Role of Flow and Endothelial Glycocalyx Integrity
Author(s) -
Ming Cheng,
Ronodeep Mitra,
Chinedu C. Okorafor,
Aliersesyan,
Ian C. Harding,
Nandita N. Bal,
Rajiv Kumar,
Hanjoong Jo,
Srinivas Sridhar,
Eno E. Ebong
Publication year - 2020
Publication title -
annals of biomedical engineering
Language(s) - English
Resource type - Journals
eISSN - 1573-9686
pISSN - 0090-6964
DOI - 10.1007/s10439-020-02474-4
Subject(s) - glycocalyx , endothelial stem cell , drug delivery , endothelial dysfunction , medicine , vascular permeability , cell culture , targeted drug delivery , chemistry , pharmacology , microbiology and biotechnology , pathology , cancer research , drug , immunology , in vitro , biology , biochemistry , organic chemistry , genetics
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.