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
References
Nov 25, 1982·Nature·J Israelachvili, R Pashley
Nov 10, 1998·Circulation·B StaelsJ C Fruchart
Mar 10, 1999·Biopolymers·J Y Gao, P L Dubin
Apr 20, 2000·The Journal of Clinical Investigation·M FebbraioR L Silverstein
Aug 18, 2000·Free Radical Biology & Medicine·R P PatelV M Darley-Usmar
Dec 3, 2004·Drug Discovery Today·Alaa-Eldin F NassarCaroline Clarimont
Dec 29, 2004·Biomaterials·Evangelia ChnariPrabhas V Moghe
Sep 6, 2005·Current Medical Research and Opinion·Erik Stroes
Feb 14, 2006·Biomacromolecules·Evangelia ChnariPrabhas V Moghe
Jun 14, 2006·Biomacromolecules·Evangelia ChnariPrabhas V Moghe
Mar 14, 2008·Current Pharmaceutical Design·M FlorentinM S Elisaf
Jan 23, 2009·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Beatrice A Golomb, Marcella A Evans
Mar 14, 2009·Biochimica Et Biophysica Acta·Søren N OlsenPeter Westh
Sep 1, 2009·Molecular Pharmaceutics·Tiziana MusacchioVladimir P Torchilin
Feb 23, 2010·Acta Biomaterialia·Nicole M IversonPrabhas V Moghe
Jun 26, 2010·Molecular Pharmaceutics·Thomas A DieziGlen S Kwon
Aug 6, 2011·Macromolecules·Jiao LuMolly S Shoichet
Sep 1, 2011·Pharmaceutical Research·Tobias MillerAchim Goepferich
Jul 28, 2012·Acta Biomaterialia·Sarah HehirKathryn E Uhrich
Jun 26, 2013·Biomacromolecules·Dawanne E PoreeKathryn E Uhrich
Feb 18, 2014·Polymer Chemistry·Dalia AbdelhamidKathryn E Uhrich
Jul 26, 2014·Saudi Pharmaceutical Journal : SPJ : the Official Publication of the Saudi Pharmaceutical Society·Prasad G JamkhandeRam S Sakhare
Jul 30, 2014·Biomacromolecules·Allison FaigKathryn E Uhrich
Aug 21, 2014·Accounts of Chemical Research·Li GuKathryn Uhrich
Dec 19, 2014·Circulation·Dariush MozaffarianUNKNOWN American Heart Association Statistics Committee and Stroke Statistics Subcommittee
Apr 22, 2015·Biomaterials·Dalia S AbdelhamidKathryn E Uhrich
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
Feb 3, 2018·Nanomaterials·Alysha MorettiKathryn E Uhrich
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
May 1, 2021·Nanoscale·Binyang GaoYan Luo
Mar 20, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Alysha MorettiKathryn E Uhrich
Sep 3, 2020·ACS Omega·Vicente D SamithReza Dabirian
Mar 9, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chang LiuYun Sun