title: Chitosan-interferon-β gene complex powder for inhalation treatment of lung metastasis in mice.
abstract: We prepared gene powders with chitosan as a non-viral vector and mannitol as a dry powder carrier to compare their gene expression and therapeutic efficacy to intravenous or intratracheal gene solutions using mice burdened with pulmonary metastasis prepared by injecting CT26 cells. The expression of a luciferase expression plasmid driven by the cytomegalovirus promoter (pCMV-Luc) and plasmid DNA encoding farnesylated enhanced green fluorescent protein (pEGFP-F) suggested that the genes expressed in both normal and tumorous tissues and the intratracheal powder resulted in higher expression than the intravenous or intratracheal solution. The intravenous and intratracheal solutions and the intratracheal powder of pCMV-Muβ encoding murine interferon-β were administered the day after the inoculation of mice with CT26 cells. Lung weight and the number of pulmonary nodules at day 21 were significantly suppressed by the three formulations at a dose of 10 μg (N/P = 5). Reducing the dose to 1 μg resulted in a loss of effect by the intravenous solution; however, the intratracheal formulations, especially the powder, were still effective. The intratracheal powder of pCMV-Muβ at a dose of 1 μg administered on day 1 significantly extended mean survival time compared to the untreated control. These findings showed that therapeutic gene powders are promising for gene therapy to treat lung cancer or metastasis.
authors.affiliation: Department of Drug Delivery Research, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan. okamotoh@meijo-u.ac.jp
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okamoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Shiraki
authors.forename: Reiko
authors.initials: R
authors.lastname: Yasuda
authors.forename: Kazumi
authors.initials: K
authors.lastname: Danjo
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use*; D049409:Luciferases, Firefly / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008353:Mannitol / Q000737:chemistry; D051379:Mice; D008815:Mice, Inbred Strains; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000235:genetics; D011208:Powders; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D011208:Powders; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D008353:Mannitol; D016899:Interferon-beta; D048271:Chitosan; D049409:Luciferases, Firefly