1. Micellar and structural stability of nanoscale amphiphilic polymers: Implications for anti-atherosclerotic bioactivity.
- Author
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Zhang Y, Li Q, Welsh WJ, Moghe PV, and Uhrich KE
- Subjects
- Anions, Atherosclerosis pathology, Fluorescence Resonance Energy Transfer, Humans, Lipoproteins, LDL metabolism, Macrophages drug effects, Molecular Dynamics Simulation, Monocytes pathology, Particle Size, Polymers chemical synthesis, Polymers pharmacology, Serum metabolism, Surface-Active Agents chemical synthesis, Surface-Active Agents pharmacology, Temperature, Atherosclerosis drug therapy, Micelles, Nanoparticles chemistry, Polymers chemistry, Polymers therapeutic use, Surface-Active Agents chemistry, Surface-Active Agents therapeutic use
- Abstract
Atherosclerosis, a leading cause of mortality in developed countries, is characterized by the buildup of oxidized low-density lipoprotein (oxLDL) within the vascular intima, unregulated oxLDL uptake by macrophages, and ensuing formation of arterial plaque. Amphiphilic polymers (AMPs) comprised of a branched hydrophobic domain and a hydrophilic poly(ethylene glycol) (PEG) tail have shown promising anti-atherogenic effects through direct inhibition of oxLDL uptake by macrophages. In this study, five AMPs with controlled variations were evaluated for their micellar and structural stability in the presence of serum and lipase, respectively, to develop underlying structure-atheroprotective activity relations. In parallel, molecular dynamics simulations were performed to explore the AMP conformational preferences within an aqueous environment. Notably, AMPs with ether linkages between the hydrophobic arms and sugar backbones demonstrated enhanced degradation stability and storage stability, and also elicited enhanced anti-atherogenic bioactivity. Additionally, AMPs with increased hydrophobicity elicited increased atheroprotective bioactivity in the presence of serum. These studies provide key insights for designing more serum-stable polymeric micelles as prospective cardiovascular nanotherapies., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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