Treatment of adjuvant arthritis using microencapsulated antisense NF-κB oligonucleotides.
Antisense oligonucleotides are promising new therapeutic agents used to selectively inhibit target genes such as Nuclear Factor Kappa B (NF-κB), an important transcription factor in the pathogenesis of inflammatory disease. The purpose of the present study was to evaluate microencapsulated antisense oligonucleotides specific to NF-κB for in vitro efficacy and treatment of adjuvant-induced arthritis in rats. Oligonucleotide-loaded albumin microspheres were prepared and characterized in terms of size, zeta potential, morphology and release pattern. This study reports significant NF-κB inhibition in vitro after treatment with microencapsulated antisense oligonucleotides. Furthermore, microencapsulated antisense NF-κB oligonucleotides were found to inhibit paw inflammation associated with rat adjuvant-induced arthritis in a dose-dependent manner. Taken together, the results presented in this work described albumin microspheres to be effective delivery vehicles for antisense NF-κB oligonucleotides and a potential treatment for inflammatory diseases.
Akhavein
Nima
N
College of Pharmacy and Health Sciences, Mercer University, Atlanta, Georgia, USA. nima.akhavein@student.mercer.edu
Oettinger
Carl W
CW
Gayakwad
Sanjay G
SG
Addo
Richard T
RT
Bejugam
Naveen K
NK
Bauer
John D
JD
Do
Duc
D
Pollock
Stanley H
SH
D'souza
Martin J
MJ
D000418:Albumins / Q000276:immunology / Q000633:toxicity; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000235:genetics; D002460:Cell Line; D015536:Down-Regulation; D008297:Male; D008863:Microspheres; D016328:NF-kappa B / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
D000418:Albumins; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense