AmBisome (Liposomal Amphotericin B): A Comparative Review

Boswell, Garry W.; Buell, Donald N.; Bekersky, Ihor

doi:10.1002/j.1552-4604.1998.tb04464.x

Cited by 192 publications

(116 citation statements)

References 15 publications

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“…Compared with other lipid formulations of AMB, rHDLs possess unique properties that may be exploited in creating a second generation or designer rHDLs to achieve enhanced efficacy. In terms of bioavailability, it is known that commercial liposomal AMB was engineered to possess slow AMB release kinetics (29). This property, which is not shared by AMB-rHDL, may explain the effectiveness of AMB-rHDL in in vitro pathogenic fungi growth inhibition assays.…”

Section: Amb-rhdl Efficacy In the Treatment Of Systemic Candidiasismentioning

confidence: 99%

Reconstituted high density lipoprotein enriched with the polyene antibiotic amphotericin B

Oda¹,

Hargreaves²,

Beckstead³

et al. 2006

Journal of Lipid Research

102

103

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The polyene antibiotic amphotericin B (AMB) is an effective antifungal agent whose therapeutic potential is limited by poor aqueous solubility and toxicity toward host tissues. Addition of apolipoprotein A-I to a multilamellar phospholipid vesicle dispersion containing 20% (w/w) AMB induces the formation of reconstituted high density lipoprotein (rHDL), with solubilization of the antibiotic. Density gradient ultracentrifugation resulted in flotation of the complexes to a density of 1.16 g/ml, and negative stain electron microscopy revealed a population of disk-shaped particles. Native gradient polyacrylamide gel electrophoresis indicated a particle diameter of z8.5 nm. Absorbance spectroscopy provided evidence for AMB integration into the lipid milieu. AMB-rHDLs were potent inhibitors of Saccharomyces cerevisiae growth, yielding 90% growth inhibition at ,1 mg/ml yeast culture. In studies with pathogenic fungal species, similar growth inhibition characteristics were observed. Compared with AMB-deoxycholate micelles, AMB-rHDL displayed greatly attenuated red blood cell hemolytic activity and decreased toxicity toward cultured hepatoma cells. In in vivo studies in immunocompetent mice, AMB-rHDLs were nontoxic at 10 mg/kg, and they showed efficacy in a mouse model of candidiasis at concentrations as low as 0.25 mg/kg. These results indicate that AMB-rHDLs constitute a novel formulation that effectively solubilizes the antibiotic and elicits strong in vitro and in vivo antifungal activity with no observed toxicity at therapeutic

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Section: Amb-rhdl Efficacy In the Treatment Of Systemic Candidiasismentioning

confidence: 99%

Reconstituted high density lipoprotein enriched with the polyene antibiotic amphotericin B

Oda¹,

Hargreaves²,

Beckstead³

et al. 2006

Journal of Lipid Research

102

103

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“…To induce temporary leucopenia, cyclophosphamide (Shionogi & Co., Ltd., Osaka, Japan) was administered subcutaneously at a dose of 200 and 100 mg/kg 2 days before and 1 day after infection, respectively. Mice were infected with 0.2 ml of the cell suspensions via the tail veins (3ϫ10 5 to 5ϫ10 5 CFU/mouse). Fungal burden in the blood and kidney.…”

mentioning

confidence: 99%

Evaluation of Antifungal Pharmacodynamic Characteristics of AmBisome against Candida albicans

Koji

Yamamoto

Ueda

2006

Microbiology and Immunology

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Amphotericin B (AMB) has been historically considered the 'gold standard' therapy for systemic fungal infections (14). In a pharmacodynamic profile, AMB exhibits concentration-dependent antifungal activity (4,11). On the other hand, AMB has a wide variety of acute and chronic side effects, and in particular, dosedependent nephrotoxicity has limited its use (8). Thus, the therapeutic dose is often determined by renal tolerance rather than infection severity.To reduce AMB toxicity, a liposomal formulation of AMB (AmBisome), comprising small unilamellar vesicles containing the AMB molecule, has been developed. As a consequence of AMB integration into the hydrophobic membrane, AmBisome exhibits characteristic pharmacokinetics of a liposome, and has pharmacological profiles and toxic properties different from those of AMB (1, 2, 5, 6). Although AmBisome possesses an antifungal activity, it is not clear whether it exhibits the same pharmacodynamic properties as AMB. Therefore, in this study, we conducted a timekill curve study with AmBisome and AMB deoxycholate (Fungizone) against Candida albicans in an effort to characterize the relationship between the concentration and in vitro antifungal activity, and characterized the pharmacokinetic/pharmacodynamic (PK/PD) parameter predictive of the in vivo efficacy of AmBisome in a leucopenic mouse model of disseminated candidiasis. Materials and Methods

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“…El ambisome es un liposoma esférico, pequeño, unilamelar, con un tamaño promedio de 80 nm 8,9 y permanece como una esfera intacta y estable por períodos prolongados dentro del organismo, lo que le otorga propiedades farmacocinéticas diferentes a las otras formulaciones lípidicas, entre las que se encuentra menor clearance y mayor duración de la concentra-ción plasmática óptima 9 . El liposoma se acumularía en el sitio de infección y su disrupción ocurriría luego de estar adherido a la pared celular del hongo, lo que resultaría en la unión de la anfotericina B con el ergosterol de la membrana celular y en la subsecuente lisis celular.…”

Section: Discussionunclassified

Terapéutica de apoyo en la mucormicosis

E²,

2006

Rev. Otorrinolaringol. Cir. Cabeza Cuello

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RESUMENLa mucormicosis es una infección infrecuente, causada por hongos oportunistas, pertenecientes al orden de los mucorales, cuyo sello es la invasión vascular por hifas, que conduce a la trombosis arterial. Generalmente afecta a pacientes con una enfermedad de base y produce una infección invasiva, frecuentemente fulminante.A continuación analizamos el caso de un paciente de 13 años con leucemia linfática aguda y neutropenia secundaria a la quimioterapia, cuyo cuadro clínico se presentó con cefalea fiebre y rinorrea. Las imágenes evidenciaron un compromiso de la pared lateral del seno esfenoidal. Fue tratado con Anfotericina B liposomal, factor de crecimiento de neutrófilos y resección quirúrgica en dos oportunidades con buena respuesta clínica y radiológica.Palabras clave: mucormicosis, anfotericina B liposomal, factor de crecimiento de neutrófilos. SUMMARYMucormycosis is an infrequent infection, caused by opportunistic fungi, that belong to the order of the mucorals, whose seal is vascular invasion through hypha, and that leads to arterial thrombosis. It generally affects patients with a basic disease and produces an invasive infection, which is frequently fulminating.We will now analyze the case of a 13 year old patient suffering from acute lymphatic leukemia and neutropenia secondary to chemotherapy, whose clinical picture is migraine, fever and rhynorrea. The images showed a compromise of the lateral wall of the sphenoidal cavity. He was treated with liposomal Amphotericin B, neutrophile growth factor and surgical resection in two opportunities with good clinical and radiological response.

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AmBisome (Liposomal Amphotericin B): A Comparative Review

Cited by 192 publications

References 15 publications

Reconstituted high density lipoprotein enriched with the polyene antibiotic amphotericin B

Reconstituted high density lipoprotein enriched with the polyene antibiotic amphotericin B

Evaluation of Antifungal Pharmacodynamic Characteristics of AmBisome against Candida albicans

Terapéutica de apoyo en la mucormicosis

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