RESUMEN
The effects of emulsome nanosize range lipid particles containing amphotericin B (EAmB) were compared with the reference formulation containing deoxycholate (Fungizone; Bristol-Myers Squibb, Munich, Germany) and with the commercial amphotericin lipid complex preparation (AmBisome; Nexstar, San Dimas, CA, USA). The minimal inhibitory concentrations of Fungizone and EAmB were identical although killing of Candida albicans was delayed when EAmB was used. In a tissue culture model and in mice, the incorporation of AmB into emulsomes resulted in a considerable reduction of toxicity in comparison with Fungizone. For comparison of the in vivo effect of the preparations a mouse model of systemic infection with C. albicans was used. All preparations were able to reduce the fungal burden in the liver and kidneys in comparison with control animals treated with isotonic saline. AmBisome was more efficient in the reduction of the fungal burden of the liver than EAmB and Fungizone, even when applied in a similar dosage of 1 mg kg(-1). In the kidneys, EAmB and Fungizone was slightly more effective than AmBisome. Therefore, in our models, the incorporation of AmB into nanosize particles was able to reduce toxicity without loss of efficiency. EAmB may be considered a candidate preparation for the treatment of infections with C. albicans in humans.
Asunto(s)
Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Candidiasis/tratamiento farmacológico , Fungemia/tratamiento farmacológico , Anfotericina B/farmacocinética , Anfotericina B/toxicidad , Animales , Antifúngicos/farmacocinética , Antifúngicos/toxicidad , Candida/efectos de los fármacos , Candidiasis/metabolismo , Candidiasis/microbiología , Técnicas de Cultivo de Célula , Femenino , Fungemia/microbiología , Interleucinas/metabolismo , Lípidos , Liposomas , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Suspensiones , Distribución TisularRESUMEN
Intranasal immunization of mice with human immunodeficiency virus (HIV) rgp160 complexed to proteosomes improved anti-gp160 serum IgA and IgG titers, increased the number of gp160 peptides recognized, and stimulated anti-gp160 intestinal IgA compared with immunization with uncomplexed rgp160 in saline. These enhanced responses were especially evident when either a bioadhesive nanoemulsion (emulsomes) or cholera toxin B subunit (CTB) was added to the proteosome-rgp160 vaccine. Furthermore, anti-gp160 IgG and IgA in vaginal secretions and fecal extracts were induced after intranasal immunization with proteosome-rgp160 delivered either in saline or with emulsomes. Formulation of uncomplexed rgp160 with emulsomes or CTB also enhanced serum and selected mucosal IgA responses. Induction of serum, vaginal, bronchial, intestinal, and fecal IgA and IgG by intranasal proteosome-rgp160 vaccines delivered in saline or with emulsomes or CTB is encouraging for mucosal vaccine development to help control the spread of HIV transmission and AIDS.
Asunto(s)
Portadores de Fármacos , Proteínas gp160 de Envoltorio del VIH/administración & dosificación , Proteínas gp160 de Envoltorio del VIH/inmunología , Inmunización/métodos , Nariz/inmunología , Vacunas Sintéticas/inmunología , Administración Intranasal , Animales , Sangre/inmunología , Toxina del Cólera , Emulsiones , Femenino , Anticuerpos Anti-VIH/inmunología , Inmunidad Mucosa , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Intestinos/inmunología , Pulmón/inmunología , Ratones , Ratones Endogámicos BALB C , Proteínas , Vacunas Sintéticas/administración & dosificación , Vagina/inmunologíaRESUMEN
PURPOSE: Desmopressin acetate (DDAVP) is used parenterally and intranasally in the control of several diseases. Oral administration of DDAVP, while most desirable, is not practical presently due to low bioavailability. The objective of the present study was to explore the feasibility for employing oil-in-water MucoAdhesive SubMicron Emulsion (MA-SME), a novel mucoadhesive vehicle with polymer-coated droplets, for enhanced oral delivery of DDAVP. METHODS: We used a modified pharmacopeal method, based on measurement of the antidiuretic activity, for the assessment of oral delivery of DDAVP in rats. DDAVP formulated in two MA-SME preparations, in non-mucoadhesive SME (plain-SME), in saline and in other control solutions was administered orally to rats via a stomach tube at a dose of 0.5 units/kg. At various times following DDAVP administration, water was given via a stomach tube. Excretion times for 30% and 60% of the total water load were measured. RESULTS: Excretion times for DDAVP in MA-SME formulations were always longer (up to 2-fold) than those following DDAVP in saline. By contrast, excretion times for DDAVP in plain-SME and in non-SME Carbopol (a Mucoadhesive polymer) solution were virtually identical to those for DDAVP in saline. CONCLUSIONS: Formulations of MA-SME were shown to generate substantial enhancement (up to 12-fold) of the rat oral bioavailability of DDAVP with regard to simple saline solution of the drug. From the results it is also evident that MA-SME, but not plain-SME or non-SME Carbopol solution, is responsible for the enhancement of oral delivery of DDAVP in rats.