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

Biomaterials
Yingyue ZhangKathryn E Uhrich

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 ...Continue Reading

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Citations

Aug 4, 2016·Journal of Colloid and Interface Science·Yingyue ZhangKathryn E Uhrich
Aug 16, 2016·Nanomedicine : Nanotechnology, Biology, and Medicine·Yingyue ZhangKathryn E Uhrich
Aug 19, 2016·Advanced Drug Delivery Reviews·Handan AcarMatthew Tirrell
Mar 7, 2018·International Journal of Molecular Sciences·Nemany Abdelhamid Nemany HanafyStefano Leporatti
Jun 29, 2018·Small·Linda C NoukeuKytai T Nguyen
Mar 7, 2018·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Zhibin LiPaul K Chu
Jan 12, 2021·Advanced Drug Delivery Reviews·Jun ChenHo-Wook Jun
Jan 7, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hongliang HeHu Yang
Mar 9, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chang LiuYun Sun

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