title: Pro-inflammatory cytokine inhibition in the primate using microencapsulated antisense oligomers to NF-kappaB.
abstract: OBJECTIVE
  Antisense oligomers to NF-kappaB (ASO) were incorporated into albumin microspheres to determine if microcapsules containing ASO inhibit pro-inflammatory cytokines to a greater extent than comparable doses of ASO in solution. Phagocytosis of microcapsules and intracellular release of ASO in macrophages was evaluated.
  
  
  METHODS
  Comparable doses of microencapsulated ASO and ASO in solution were evaluated in non-human primates.
  
  
  METHODS
  Blood was sampled and stimulated with Escherichia coli endotoxin ex vivo. TNF, IL-1 and IL-6 concentrations were compared for 72 hrs. The intracellular concentration of ASO was measured in macrophages in vitro to evaluate the difference in intracellular penetration of microencapsulated ASO.
  
  
  RESULTS
  Microencapsulated ASO produced significantly greater cytokine inhibition at all time points compared to ASO in solution. There were no side effects to ASO in the baboons. Intracellular ASO concentration was 10 fold greater in macrophages using microencapsulation.
  
  
  CONCLUSIONS
  Microencapsulated ASO to NF-kappaB is more effective than ASO in solution in pro-inflammatory cytokine inhibition in non-human primates.
authors.affiliation: College of Pharmacy and Health Sciences, Mercer University, Atlanta, GA, USA. coettinger@aol.com
authors.forename: Carl W
authors.initials: CW
authors.lastname: Oettinger
authors.forename: Martin J
authors.initials: MJ
authors.lastname: D'souza
authors.forename: Nima
authors.initials: N
authors.lastname: Akhavein
authors.forename: Glenn T
authors.initials: GT
authors.lastname: Peer
authors.forename: Fletcher B
authors.initials: FB
authors.lastname: Taylor
authors.forename: Gary T
authors.initials: GT
authors.lastname: Kinasewitz
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002214:Capsules; D016207:Cytokines / Q000037:antagonists & inhibitors*; D004655:Emulsions; D007249:Inflammation / Q000503:physiopathology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008863:Microspheres; D016328:NF-kappa B / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010215:Papio; D012710:Serum Albumin, Bovine
chemical_list: D002214:Capsules; D016207:Cytokines; D004655:Emulsions; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D012710:Serum Albumin, Bovine