title: Efficient gene silencing in lungs and liver using imidazole-modified chitosan as a nanocarrier for small interfering RNA.
abstract: Despite high specificity and potency, small interfering RNA (siRNA)-based therapeutics have been limited by their poor biostability and intracellular penetration. Thus, effective nanocarriers that can protect and efficiently deliver siRNA to target cells in vivo are needed. Here we report on the efficiency of imidazole-modified chitosan (chitosan-imidazole-4-acetic acid [IAA])-siRNA nanoparticles to mediate gene silencing after administration via either intravenous (i.v.) or intranasal (i.n.) routes. Poly(ethylene glycol) (PEG)ylated nanoparticles for i.v. delivery demonstrated significant knockdown of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) enzyme in both lung and liver at as low as 1 mg/kg siRNA dose. In addition, the efficient, dose-dependent silencing of apolipoprotein B in the liver was also shown. For i.n. delivery, significant silencing of GAPDH protein expression was seen in the lungs with only 0.5 mg/kg/day siRNA delivered over 3 consecutive days. In summary, imidazole-modified chitosan-IAA nanoparticles are potentially effective carriers for siRNA delivery.
authors.affiliation: Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712-0238, USA.
authors.forename: Bilal
authors.initials: B
authors.lastname: Ghosn
authors.forename: Ankur
authors.initials: A
authors.lastname: Singh
authors.forename: Mu
authors.initials: M
authors.lastname: Li
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Vlassov
authors.forename: Chris
authors.initials: C
authors.lastname: Burnett
authors.forename: Nitin
authors.initials: N
authors.lastname: Puri
authors.forename: Krishnendu
authors.initials: K
authors.lastname: Roy
mesh_terms: D000818:Animals; D048271:Chitosan / Q000008:administration & dosage*; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D048271:Chitosan; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases