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Micellar and structural stability of nanoscale amphiphilic polymers: Implications for anti-atherosclerotic bioactivity.

Authors
  • Zhang, Yingyue1
  • Li, Qi2
  • Welsh, William J3
  • Moghe, Prabhas V2
  • Uhrich, Kathryn E4
  • 1 Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
  • 2 Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA.
  • 3 Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, New Brunswick 08901, USA.
  • 4 Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA; Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: [email protected]
Type
Published Article
Journal
Biomaterials
Publication Date
Apr 01, 2016
Volume
84
Pages
230–240
Identifiers
DOI: 10.1016/j.biomaterials.2015.12.028
PMID: 26828687
Source
Medline
Keywords
License
Unknown

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.

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