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

Neil Patel, Richard T. Addo, Ruhi Ubale, Mohammed Nasir Uddin, Martin D'Souza, Lynetta Jobe

Research output: Contribution to journalArticle

4 Scopus citations

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. Purpose: 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. Conclusion: This treatment was successful in curbing ventricular remodeling by suppressing NF-κB activation.

Original languageEnglish (US)
Pages (from-to)796-804
Number of pages9
JournalJournal of Drug Targeting
Volume22
Issue number9
DOIs
StatePublished - Nov 1 2014

Keywords

  • Albumin microspheres
  • Antisense
  • Chronic volume overload
  • Drug delivery
  • Heart failure
  • Myocardial left ventricular remodeling
  • NF-kB
  • Spray-drying
  • Sustained release

ASJC Scopus subject areas

  • Pharmaceutical Science

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