title: The effect of antisense to NF-κB in an albumin microsphere formulation on the progression of left-ventricular remodeling associated with chronic volume overload in rats.
abstract: BACKGROUND
  Increased NF-κB levels play a crucial role in the pathophysiology of heart failure and are known to cause ventricular remodeling. Antisense therapy can be used for blocking the expression of NF-κB and subsequently avoiding heart failure. However, as with most biotechnology products, molecular instability and overall cost are often the major issues and concerns limiting the advancement of most antisense drugs to the market. Therefore, a cost-efficient biodegradable sustained release particle drug delivery system to transport and target NF-kB antisense to its intended site of action would be ideal.
  
  
  OBJECTIVE
  To evaluate the in vivo performance of a sustained release spray-dried albumin microsphere formulation for effective delivery and treatment of left ventricular remodeling with antisense to NF-κB.
  
  
  METHODS
  Albumin-based microspheres encapsulating antisense to NF-kB were prepared by spray drying and studied in a rat model to treat congestive heart failure.
  
  
  RESULTS
  The NF-κB activation and TNF-α release seen in treated animals were significantly lower than control animals. Ventricular remodeling was controlled in animals with antisense-treated AV fistulas as ΔV0-25 and ΔV0 were significantly lower compared to animals with untreated AV fistulas.
  
  
  CONCLUSIONS
  This treatment was successful in curbing ventricular remodeling by suppressing NF-κB activation.
authors.affiliation: Sullivan University College of Pharmacy , Louisville, KY , USA .
authors.forename: Neil
authors.initials: N
authors.lastname: Patel
authors.forename: Richard T
authors.initials: RT
authors.lastname: Addo
authors.forename: Ruhi
authors.initials: R
authors.lastname: Ubale
authors.forename: Mohammed Nasir
authors.initials: MN
authors.lastname: Uddin
authors.forename: Martin
authors.initials: M
authors.lastname: D'Souza
authors.forename: Lynetta
authors.initials: L
authors.lastname: Jobe
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D018450:Disease Progression; D016503:Drug Delivery Systems / Q000379:methods*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008863:Microspheres; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
chemical_list: D003692:Delayed-Action Preparations; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D014409:Tumor Necrosis Factor-alpha; D012710:Serum Albumin, Bovine
keywords: Albumin microspheres; NF-kB; antisense; chronic volume overload; drug delivery; heart failure; myocardial left ventricular remodeling; spray-drying; sustained release