Creation and Simulation of Function of Claramine-Atorvastatin Coated Hyaluronic Acid Nanoparticles for Targeted Dissolution of Atherosclerotic Plaque

Overview

Atherosclerosis, the buildup of lipids as a plaque within the inner lining of the blood vessel wall, leading to reduced vessel flexibility, is the result of a cut in the layer of activated endothelial cells, allowing for the accumulation of lipids and foam cells within the artery. It is common and eventually causes myocardial infarction and strokes, making it crucial to treat. As typically prescribed statins do not always work, invasive surgery is left as the only other option. Thus a novel, targeted therapeutic of claramine-atorvastatin coated hyaluronic acid (HA) nanoparticles was created in this research. First, HA was conjugated to lithocholic acid to create an amphiphilic polymer that self-assembled in aqueous conditions in nanoparticles when sonicated. These CD44 (inflammation) targeting nanoparticles were then coated with claramine, a PTP1B inhibitor, atorvastatin, as well as FITC for visualization. T o test the efficacy of these nanoparticles, THP-1 monocytes were differentiated into foam cells with lipopolysaccharides, PMA, cholesterol, and LDL. Once treated with coated nanoparticles, an 88x-decrease in cell proliferation was observed using a WST-8 assay, suggesting a decline in the creation of diseased cells and inflammation. Intracellular-fluorescence studies highlighted the nanoparticle’s selectivity only for diseased foam cells, while they did not enter healthy monocytes. In a 3D-carotid artery bifurcation model containing agar/diseased cells plaque, serum/media cholesterol levels decreased post-nanoparticle therapy, highlighted by ATR-FTIR studies. Finally, it was determined that nanoparticles are stable in aqueous solutions, pointing to their integrity until they reach the CD44 receptor for phagocytosis and drug delivery.

Competition history

• JSHS 2023 Category not listed

Resources

• National JSHS abstract book ↗

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