RESUMO
Itraconazole (ITZ)-loaded microemulsion (ME) systems for intranasal (IN) delivery were developed for the treatment of human rhinovirus serotype 1B (HRV1B) infection. ITZ was incorporated into the oil-in-water (o/w) ME formulation composed of benzyl alcohol (oil), Cremophor EL (surfactant), Solutol HS15 (cosurfactant), and water. The optimized composition of ME was determined by constructing pseudo-ternary phase diagram. ITZ ME formulation with about 150nm mean diameter and spherical shape was prepared and the solubility of ITZ in blank ME was markedly improved (up to 13.9mg/mL). The initial value of droplet size was maintained with four times dilution in the aqueous buffer and 72h incubation. Released amounts of drug from ME formulation were significantly enhanced compared to drug suspension group (p<0.05). Particularly, ITZ ME group displayed lower levels of inflammatory markers in the lung compared to ITZ suspension group after their IN administration in the HRV1B-infected mouse model (p<0.05). Developed ITZ ME formulation via IN route can be a promising candidate for the treatment of rhinovirus infection.
Assuntos
Química Farmacêutica/métodos , Itraconazol/farmacologia , Nanopartículas/química , Infecções por Picornaviridae/tratamento farmacológico , Rhinovirus/efeitos dos fármacos , Administração Intranasal , Animais , Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Antifúngicos/farmacologia , Álcool Benzílico/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Emulsões/química , Feminino , Glicerol/análogos & derivados , Glicerol/química , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Itraconazol/química , Itraconazol/imunologia , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Tamanho da Partícula , Infecções por Picornaviridae/imunologia , Infecções por Picornaviridae/virologia , Polietilenoglicóis/química , Rhinovirus/imunologia , Rhinovirus/fisiologia , Ácidos Esteáricos/química , Água/químicaRESUMO
Background. The presence of melanin in the fungal cell is a major virulence factor of the genus Sporothrix since it protects the fungal cells against the defense systems. Aims. The present study aimed to investigate the interference of melanin in the susceptibility of Sporothrix brasiliensis and Sporothrix schenckii sensu stricto to amphotericin B and itraconazole, drugs recommended as therapy for disseminated and subcutaneous sporotrichosis, respectively. Methods. Yeast cells were cultivated in minimal medium with or without l-DOPA in order to induce the production of melanin. Microdilution and killing assay methods were used to determine the antifungal activity against yeast cells with different mounts of melanin. Results. The killing assay showed that melanization protected isolates within the S. schenckii complex from amphotericin B, particularly in the lower concentrations tested. Conclusions. Studies combining amphotericin B and inhibitors of melanin are required in order to avoid this effect (AU)
Antecedentes. La presencia de melanina en la célula fúngica es un importante factor de virulencia del género Sporothrix en el proceso de infección, pues protege al hongo de la acción del sistema inmunitario. Objetivos. El objetivo del presente estudio fue investigar la interferencia de la melanina en la sensibilidad de Sporothrix brasiliensis y Sporothrix schenckii sensu stricto a la anfotericina B y el itraconazol, antifúngicos recomendados como terapia para la esporotricosis diseminada y la subcutánea, respectivamente. Métodos. Se cultivaron células en la fase levaduriforme en medio mínimo con o sin l-DOPA con el fin de inducir la producción de melanina. La valoración de la actividad antifúngica sobre células de Sporothrix con diferente contenido en melanina se realizó mediante microdilución en caldo y curvas de mortalidad. Resultados. El ensayo mostró que la melanización protege de la acción de la anfotericina B a las especies del complejo S. schenckii, particularmente en las concentraciones más bajas ensayadas. Conclusiones. Se requieren estudios de combinación entre diferentes clases de antifúngicos o de anfotericina B con inhibidores de la melanina, con el fin de disminuir o evitar este efecto (AU)
Assuntos
Interferência Viral , Sporothrix , Sporothrix/isolamento & purificação , Sporothrix/virologia , Anfotericina B/análise , Anfotericina B , Virulência , Anfotericina B/isolamento & purificação , Testes de Sensibilidade Microbiana/métodos , Sensibilidade e Especificidade , Fungos , Fungos/imunologia , Fungos/patogenicidade , Itraconazol/imunologia , Itraconazol/uso terapêuticoRESUMO
Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to Aspergillus fumigatus that occur frequently in patients with cystic fibrosis (CF). Recurrent episodes of bronchial obstruction, inflammation, and mucoid impaction occur in ABPA and results in bronchiectasis, fibrosis, and respiratory failure. The treatment of ABPA includes corticosteroids to reduce the acute inflammation and intraconazole to reduce the fungal colonization load in order to reduce lung injury. This case discusses the successful use of aerosolized amphotericin B for the treatment of ABPA in a 14-year-old patient with CF listed for lung transplant. The patient required fewer hospitalizations, and both oral corticosteroids and anti-fungal therapy were eventually stopped.
