title: Enhancement of in vivo anti-influenza virus activity of 5,7,4'-trihydroxy-8-methoxyflavone by drug delivery system using hydroxypropyl cellulose.
abstract: Enhancement of in vivo antiviral activity of 5,7,4'-trihydroxy-8-methoxyflavone (F36) against H3N2 subtype of influenza A virus by drug delivery system (DDS) with hydroxypropyl cellulose (HPC) was studied. Although in the absence of HPC F36 (0.5 mg/kg) showed no antiviral activity against mouse-adapted influenza virus A/Guizhou/54/89 (H3N2) in mice, when F36 solution containing HPC was administered intranasally 5 min after the virus inoculation, proliferation of the virus in both nasal and broncho-alveolar cavities was inhibited significantly. The relationship between concentration (0.2-0.5%) and deposition ratio of HPC was studied. When 10 microliters of fluorescein isothiocyanate (FITC)-conjugated HPC solution was administered intranasally to BALB/c mice, deposition ratio of HPC at 6 h after inoculation in nasal cavity was dependent on its concentration. The deposition ratio of HPC in broncho-alveolar cavity, however, was reversely dependent on its concentration. Anti-influenza virus activity of F36 in nasal and broncho-alveolar cavities was dependent both on the concentration and deposition ratio of HPC. HPC was most effective at 0.5% in nasal cavity and at 0.3% in broncho-alveolar cavity. These results indicate that DDS with HPC enhances the anti-influenza virus activity of F36 in vivo.
authors.affiliation: Oriental Medicine Research Center, Kitasato Institute, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nagai
authors.forename: Y
authors.initials: Y
authors.lastname: Nishibe
authors.forename: Y
authors.initials: Y
authors.lastname: Makino
authors.forename: T
authors.initials: T
authors.lastname: Tomimori
authors.forename: H
authors.initials: H
authors.lastname: Yamada
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002482:Cellulose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D009980:Influenza A virus / Q000502:physiology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009296:Nasal Cavity / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000821:virology; D014779:Virus Replication / Q000187:drug effects; D014783:Viscosity
chemical_list: D000998:Antiviral Agents; D005419:Flavonoids; C093385:5,7,4'-trihydroxy-8-methoxyflavone; D002482:Cellulose; C008079:hydroxypropylcellulose