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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.

Enhancement of in Vivo Anti-influenza Virus Activity of 5,7,4'-Trihydroxy-8-methoxyflavone by Drug Delivery System Using Hydroxypropyl Cellulose.