title: Safety profile of dextran-spermine gene delivery vector in mouse lungs.
abstract: A nano-sized polymer, dextran-spermine (D-SPM), was shown to have the capacity to deliver gene to the lung of mouse via intranasal route. In this study, assessments on the safety profile of D-SPM were performed to complement the gene expression results. African green monkey kidney fibroblast (COS-7) and human adenocarcinoma breast (MCF-7) cells transfected with D-SPM/pDNA showed massive reduction in the number of viable cells. As for in vivo study, elevated level of neutrophils was observed, despite the minimal level of pro-inflammatory cytokines (TNF-alpha, IL-12, IFN-gamma) detected in the bronchoalveolar lavage fluid (BALF) of mice treated with the D-SPM/pDNA complexes. Histology profile examinations of the lungs showed mild inflammatory responses, with inflamed areas overlap with healthy areas. Although reduction of mice weight was seen at day 1 post administration, the mice did not show any sign of abnormal behavior or physical appearance. Biodistribution study was performed to determine the ability of the D-SPM/pDNA complexes to infiltrate to other non-intended organs. The result showed that the D-SPM/pDNA complexes were only localized at the lung and no gene expression was detected in other organs or blood. In short, these results indicate that the D-SPM/pDNA exhibited mild toxicity in the mouse lungs.
authors.forename: Wendy Wai Yeng
authors.initials: WW
authors.lastname: Yeo
authors.forename: Hossein
authors.initials: H
authors.lastname: Hosseinkhani
authors.forename: Sabariah A
authors.initials: SA
authors.lastname: Rahman
authors.forename: Rozita
authors.initials: R
authors.lastname: Rosli
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Domb
authors.forename: Syahril
authors.initials: S
authors.lastname: Abdullah
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D019556:COS Cells; D002522:Chlorocebus aethiops; D003912:Dextrins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors / Q000009:adverse effects*; D008168:Lung / Q000378:metabolism*; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D013096:Spermine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D003912:Dextrins; D013096:Spermine