RESUMEN
AIMS: Sore throat (pharyngitis) is commonly treated with over-the-counter lozenges, tablets, sprays and gargles. While the efficacy of the active ingredients has been examined, less is known about the comparative efficacy of the different delivery formats. METHODS: A pilot study was initially performed, followed by an open-label, four-way crossover study in healthy volunteers to quantitatively assess the delivery efficacy of a lozenge, tablet, spray and gargle, using technetium-99m and scintigraphy as a marker of deposition and clearance of the active ingredients. RESULTS: Initial deposition in the mouth and throat combined was significantly greater for the solid dose forms (lozenge and tablet) than for the spray or gargle. Rates of clearance were initially similar for the tablet and lozenge with low levels of radioactivity present at up to 2 h. At 10 and 20 min, significantly more of the dose remained for the lozenge than for the tablet. The mouth appeared to act as a reservoir for continued clearance to the throat. DISCUSSION AND CONCLUSION: Scintigraphy is an effective means of quantifying the delivery efficiency, and hence availability, of sore throat medications. The results presented here suggest that both lozenges and tablets offer considerable advantages over sprays or gargles, both in terms of proportion of the dose delivered to the mouth and throat, combined, and clearance from these regions. These delivery formats provide fast, effective and prolonged delivery of active ingredients, highlighting their potential benefits for sore throat medication.
Asunto(s)
Preparaciones Farmacéuticas/administración & dosificación , Faringe/metabolismo , Radiofármacos , Pentetato de Tecnecio Tc 99m , Administración Oral , Aerosoles/administración & dosificación , Análisis de Varianza , Estudios Cruzados , Sistemas de Liberación de Medicamentos , Humanos , Antisépticos Bucales/administración & dosificación , Faringitis/tratamiento farmacológico , Faringe/diagnóstico por imagen , Proyectos Piloto , Cintigrafía , Radiofármacos/farmacocinética , Comprimidos/administración & dosificación , Pentetato de Tecnecio Tc 99m/farmacocinéticaRESUMEN
A mycobacterial cell wall complex prepared from the non-pathogenic microorganism Mycobacterium phlei, where mycobacterial DNA is preserved and complexed to cell wall fragments, possesses anticancer and immunomodulatory activity. DNA from a number of prokaryotes has been found to modulate the immune system and to induce cytokine synthesis. We have therefore determined whether the DNA associated with this complex has the ability to induce the synthesis of interleukin-12 (IL-12), a potent anticancer cytokine. Mycobacterial DNA complexed with cell wall fragments or DNA purified from M. phlei induced IL-12 synthesis by murine and human monocytes and macrophages in vitro, and was capable of inducing IL-12 synthesis in vivo in mice following i.p. administration. Neutralization of DNA with cationic liposomes or digestion with DNase I significantly decreased the ability of the cell wall complex to induce IL-12. CpG methylation of DNA extracted from these cell walls or from M. phlei did not affect the induction of IL-12 synthesis by monocytes and macrophages. In contrast, CpG methylation of DNA from Escherichia coli abolished its ability to induce IL-12 synthesis. These results demonstrate that unmethylated CpG motifs present in M. phlei DNA are not a prerequisite for the induction of IL-12 synthesis. The size of the mycobacterial DNA, in the range of 5 bp to genomic DNA, did not influence its capacity to induce IL-12. Our results emphasize that M. phlei DNA associated with the cell wall complex makes a significant contribution to the overall immunomodulatory and anticancer activity of this mycobacterial cell wall preparation and that these activities are not correlated with the presence of CpG motifs.