title: Chitosan/TPP-hyaluronic acid nanoparticles: a new vehicle for gene delivery to the spinal cord.
abstract: Gene delivery offers therapeutic promise for the treatment of neurological diseases and spinal cord injury. Several studies have offered viral vectors as vehicles to deliver therapeutic agents, yet their toxicity and immunogenicity, along with the cost of their large-scale formulation, limits their clinical use. As such, non-viral vectors are attractive in that they offer improved safety profiles compared to viruses. Poly(ethylene imine) (PEI) is one of the most extensively studied non-viral vectors, but its clinical value is limited y its cytotoxicity. Recently, chitosan/DNA complex nanoparticles have een considered as a vector for gene delivery. Here, we demonstrate that DNA nanoparticles made of hyaluronic acid (HA) and chitosan have low cytotoxicity and induce high transgene expression in neural stem cells and organotypic spinal cord slice tissue. Chitosan-TPP/HA nanoparticles were significantly less cytotoxic than PEI at various concentrations. Additionally, chitosan-TPP/HA nanoparticles with pDNA induced higher transgene expression in vitro for a longer duration than PEI in neural stem cells. These results suggest chitosan-TPP/HA nanoparticles may have the potential to serve as an option for gene delivery to the spinal cord.
authors.affiliation: a Spine & Spinal Cord Institute, Department of Neurosurgery, Yonsei University College of Medicine , 120-752, 134 Shinchon-dong , Seodaemoon-gu , Seoul , South Korea.
authors.forename: So-Jung
authors.initials: SJ
authors.lastname: Gwak
authors.forename: Jong Kwon
authors.initials: JK
authors.lastname: Jung
authors.forename: Sung Su
authors.initials: SS
authors.lastname: An
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Oh
authors.forename: William A
authors.initials: WA
authors.lastname: Pennant
authors.forename: Hye Yeong
authors.initials: HY
authors.lastname: Lee
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Kong
authors.forename: Keung Nyun
authors.initials: KN
authors.lastname: Kim
authors.forename: Do Heum
authors.initials: DH
authors.lastname: Yoon
authors.forename: Yoon
authors.initials: Y
authors.lastname: Ha
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques / Q000295:instrumentation; D006571:Heterocyclic Compounds / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D058953:Neural Stem Cells / Q000502:physiology; D009943:Organophosphorus Compounds / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000502:physiology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy; D046509:Tissue Culture Techniques
chemical_list: D006571:Heterocyclic Compounds; D009943:Organophosphorus Compounds; C528765:tris(o-phenylenedioxy)cyclotriphosphazene; D006820:Hyaluronic Acid; D004247:DNA; D048271:Chitosan