title: Tethered polymer nanoassemblies for sustained carfilzomib release and prolonged suppression of proteasome activity.
abstract: Proteasome inhibitors, such as carfilzomib (CFZ), have shown potential to treat various types of cancers in preclinical models, but clinical applications are limited likely due to formulation and delivery issues. Results & methodology: Tethered polymer nanoassemblies (TNAs) were synthesized by tethering hydrophilic polymers and hydrophobic groups to charged polymer scaffolds, and then end-capping remaining amines on scaffold. Drug entrapment and drug release half-lives increased as charge was removed from scaffold. TNAs with sustained CFZ release maintained drug efficacy after preincubation and increased duration of proteasome inhibition in cancer cells compared with free CFZ.
  
  
  
  TNAs fine-tuned CFZ release as charge was removed from polymer scaffold, which allowed for sustained proteasome inhibition in cancer cells and potentially enhanced anticancer efficacy.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, KY 40536-0596, USA.
authors: Derek
authors: D
authors: Reichel
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, KY 40536-0596, USA.
authors: Min Jae
authors: MJ
authors: Lee
authors: College of Pharmacy, Seoul National University, 1 Gwanak-Ro, Gwanak-Gu, Seoul 151-742, Korea.
authors: Wooin
authors: W
authors: Lee
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, KY 40536-0596, USA.
authors: Kyung Bo
authors: KB
authors: Kim
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, KY 40536-0596, USA.
authors: Younsoo
authors: Y
authors: Bae
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D065546:Drug Liberation; D004355:Drug Stability; D006801:Humans; D020128:Inhibitory Concentration 50; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D003692:Delayed-Action Preparations; D009842:Oligopeptides; D011108:Polymers; D061988:Proteasome Inhibitors; C524865:carfilzomib; D046988:Proteasome Endopeptidase Complex
keywords: cancer chemotherapy; controlled release; nanoparticles; proteasome inhibitors; solid cancers