title: Enhanced bioavailability of orally administered antisense oligonucleotide to nuclear factor kappa B mRNA after microencapsulation with albumin.
abstract: Antisense molecules that pertain to ribonucleic acid (RNA) and complementary to the messenger RNA (mRNA) are produced by transcription of a given gene. Antisense oligonucleotides have emerged as potential gene-specific therapeutic agents that are currently undergoing evaluation in clinical trials for a variety of diseases. When administered orally, antisense oligionucleotides have poor bioavailability as they are rapidly degraded by the acid in the stomach and by the enzymes in the intestine. Therefore, the enhancement of bioavailability after oral administration is highly desirable. This article shows the enhanced bioavailability of antisense oligonucleotides that targets nuclear factor kappa B (NF-κB) mRNA after encapsulating in an inert, biodegradable albumin polymer matrix that was administered via the oral route into a rat model. The bioavailability of the antisense oligonucleotides to NF-κB in microencapsulated form was compared to the solution form of the drug upon oral administration. The solution form had a low bioavailability of 9%, whereas the bioavailability for the microencapsulated form of the drug increased up to 70%. Moreover, the other pharmacokinetic parameters including half-life (t1/2) and volume of distribution (Vd) increased for the microencapsulated form compared to the solution form of the drug.
authors.affiliation: School of Pharmacy, Lake Erie College of Osteopathic Medicine, Erie, PA, USA.
authors.forename: Mohammad Nasir
authors.initials: MN
authors.lastname: Uddin
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Patel
authors.forename: Tuhin
authors.initials: T
authors.lastname: Bhowmik
authors.forename: Bernadette
authors.initials: B
authors.lastname: D'Souza
authors.forename: Archana
authors.initials: A
authors.lastname: Akalkotkar
authors.forename: Frank
authors.initials: F
authors.lastname: Etzlar
authors.forename: Carl William
authors.initials: CW
authors.lastname: Oettinger
authors.forename: Martin
authors.initials: M
authors.lastname: D'Souza
mesh_terms: D000284:Administration, Oral; D000418:Albumins / Q000737:chemistry*; D000818:Animals; D001682:Biological Availability; D004339:Drug Compounding / Q000379:methods; D005260:Female; D006207:Half-Life; D008863:Microspheres; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000418:Albumins; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger