In-vitro antifungal activity of liposomal nystatin in comparison with nystatin, amphotericin B cholesteryl sulphate, liposomal amphotericin B, amphotericin B lipid complex, amphotericin B desoxycholate, fluconazole and itraconazole

Carrillo-Muñoz, Alfonso Javier; Quindós, Guillermo; Tur, C; Ruesga, María Teresa; Miranda, Y.; Valle, Oscar del; Cossum, Paul A.; Wallace, T L

doi:10.1093/jac/44.3.397

Cited by 78 publications

(42 citation statements)

References 5 publications

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“…Since both techniques produced similar internalization rates with A549 cells, we were confident that the nystatin protection assay gave an accurate and objective measurement of invasion. This technique is simple and sensitive and should be applicable to other pathogenic fungi as nystatin is fungicidal toward both C. albicans and C. neoformans (6). Furthermore, comparing the results of immunostaining and nystatin protection may provide quantitative information on the extent of killing by host cells.…”

Section: Discussionmentioning

confidence: 99%

Uptake ofAspergillus fumigatusConidia by Phagocytic and Nonphagocytic Cells In Vitro: Quantitation Using Strains Expressing Green Fluorescent Protein

Wasylnka¹,

2002

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Several pathogenic fungal organisms enter eukaryotic cells and manipulate the host cell environment to favor their own growth and survival. Aspergillus fumigatus is a saprophytic fungus that causes invasive lung disease in the immunocompromised host. To determine whether A. fumigatus could enter eukaryotic cells, we studied the uptake of two different GFP-expressing A. fumigatus strains into A549 lung epithelial cells, human umbilical vein endothelial (HUVE) cells, and J774 murine macrophages in vitro. A549 cells internalized 30% of the bound conidia whereas HUVE and J774 cells internalized 50 and 90%, respectively. Conidia within A549 cells remained viable for 6 h; however, 60 to 80% of conidia within J774 cells were killed after only 4 h. Live and heat-killed conidia were internalized to the same extent by A549 cells. After 6 h, almost none of the conidia inside A549 cells had germinated, whereas extracellular conidia had developed germ tubes. Internalization of conidia by A549 cells was a temperature-dependent process and required rearrangement of the underlying host cell cytoskeleton; uptake was inhibited by 75% with 0.5 M cytochalasin D and by 65% with 5 M colchicine. Fluorescent labeling of infected A549 cells with rhodamine phalloidin provided visible evidence of cytoskeletal alteration as many of the intracellular conidia were contained in actin-coated phagosomes. These data provide evidence that significant numbers of A. fumigatus conidia can be internalized by nonprofessional phagocytes in vitro and these cells may serve as reservoirs for immune cell evasion and dissemination throughout the host.

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Section: Discussionmentioning

confidence: 99%

Uptake ofAspergillus fumigatusConidia by Phagocytic and Nonphagocytic Cells In Vitro: Quantitation Using Strains Expressing Green Fluorescent Protein

Wasylnka¹,

2002

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“…This was tested by spread plate method, in order to establish the minimum inhibitory concentration (MIC) at which the extracted fluconazole could prevent the fungal growth. The reported MIC 50 value of fluconazole against C. albicans was 0.5 μg/ml and MIC ranges from 0.125 to >64 μg/ml (37). Although the MIC 50 value obtained with the fluconazole-loaded microspheres was comparatively higher (5.69 μg/ml), the lowest concentration (1.29 μg/ml) at which a definite decrease in colony count was observed was in good agreement with the reported MIC range and even this concentration could be achieved within half an hour following dissolution of the microspheres.…”

Section: Effect Of External Aqueous Phase Volumementioning

confidence: 99%

Investigation on Processing Variables for the Preparation of Fluconazole-Loaded Ethyl Cellulose Microspheres by Modified Multiple Emulsion Technique

Maiti¹,

Dey²,

Kaity³

et al. 2009

AAPS PharmSciTech

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Abstract. Fluconazole-loaded ethyl cellulose microspheres were prepared by alginate facilitated (water-in-oil)-in-water emulsion technology and the effects of various processing variables on the properties of microspheres were investigated. Scanning electron microscopy revealed spherical nature and smooth surface morphology of the microspheres except those prepared at higher concentration of emulsifiers and higher stirring speeds. The size of microspheres varied between 228 and 592 μm, and as high as 80% drug entrapment efficiency was obtained depending upon the processing variables. When compared up to 2 h, the drug release in pH 1.2 HCl solution was slower than in pH 7.4 phosphate buffer saline solution. However, this trend was reversed at high shear conditions. The microspheres provided extended drug release in alkaline dissolution medium and the drug release was found to be controlled by Fickian-diffusion mechanism. However, the mechanism shifted to anomalous diffusion at high shear rates and emulsifier concentrations. The aging of microspheres did not influence the drug release kinetics. However, the physical interaction between drug and excipients affected the drug dissolution behaviors. X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC) analysis revealed amorphous nature of drug in the microspheres. Fourier transform infrared (FTIR) spectroscopy indicated stable character of fluconazole in the microspheres. The stability testing data also supported the stable nature of fluconazole in the microspheres. The fluconazole extracted from 80% drug-loaded formulation showed good in vitro antifungal activity against Candida albicans. Thus, proper control of the processing variables involved in this modified multiple emulsion technology could allow effective incorporation of slightly water soluble drugs into ethyl cellulose microspheres without affecting drug stability.KEY WORDS: entrapment efficiency; ethyl cellulose; fluconazole; microspheres; water-in-oil-in-water (w/o/w) multiple emulsion.

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“…F-88, p. 161,1997). This has prompted new investigations of its antifungal properties and spectrum as well as its physicochemical and pharmacokinetic characteristics (5,7,11,15; S. Arikan, M. Lozano-Chiu, V. Paetznick, D. Gordon, T. Wallace, and J. H. Rex, Abstr. 98th Gen. Meet.…”

mentioning

confidence: 99%

Differential Antifungal Activity of Isomeric Forms of Nystatin

Ostrosky-Zeichner

Bazemore

Paetznick

et al. 2001

Antimicrob Agents Chemother

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When nystatin is placed in RPMI and other biological fluids, there is loss of pure nystatin, with the development of two distinguishable chromatographic peaks, 1 and 2. Peak 1 appears identical to commercially prepared nystatin. By nuclear magnetic resonance (NMR) and mass spectral analysis, peak 2 appears to be an isomer of peak 1. The isomers are quantitatively and fully interconvertible. Formation of peak 2 is accelerated at a pH of >7.0 and ultimately reaches a near 55:45 (peak 1/peak 2 ratio) mixture. We sought to determine the relative activities of peaks 1 and 2 against Candida spp. Peak 2 consistently showed higher MICs when it was the predominant form during the experiment. Time-kill analyses showed that peak 2 required >8؋ the concentration of peak 1 to produce a modest and delayed killing effect, which was never of the same magnitude as that produced by peak 1. In both types of assays, the activity of peak 2 corresponded with intra-assay formation of peak 1. Both MIC measurements and time-kill analysis suggest that peak 2 has considerably less activity, if any at all, against Candida spp. Peak 2 may serve as a reservoir for peak 1.Life-threatening fungal infections have become increasingly prevalent among patients with human immunodeficiency virus or AIDS, patients with cancer, transplant recipients, and patients in intensive care units (1, 2-4, 6, 10). Therapeutic options are often limited by the toxicity of currently available systemic antifungal agents and the emergence of resistance (9,24,25). This has prompted the development of new antifungal agents, as well as the "rediscovery" and "reengineering" of agents where use had been limited due to toxicity (16).Nystatin is a polyene-macrolide antifungal antibiotic produced by Streptomyces noursei that was discovered and developed in the 1950s (18). It is now widely available for the topical treatment of localized fungal infections. Toxicity problems prevented its use as a systemic agent, but recently developed liposomal delivery technologies have made it an attractive candidate for the treatment of severe systemic fungal infections (12,16,17,20,26; C. J. Jessup, T. J. Wallace, and M. A. Ghannoum, 37th Intersci. Conf. Antimicrob. Agents Chemother., abstr. F-88, p. 161, 1997). This has prompted new investigations of its antifungal properties and spectrum as well as its physicochemical and pharmacokinetic characteristics (5, 7, 11, 15; S. Arikan, M. Lozano-Chiu, V. Paetznick, D. Gordon, T. Wallace, and J. H. Rex, Abstr. 98th Gen. Meet. Am. Society Microbiol., abstr. C-280, p. 178, 1998).Commercially prepared nystatin appears as a single, highly pure chromatographic peak (hereinafter referred as peak 1) while in an organic solvent. However, when placed in a biological matrix, such as human plasma or culture medium, chromatographic analysis yields a second peak that elutes after the pure peak seen from nystatin stored in an organic solvent. Earlier work (data on file at Aronex Pharmaceuticals) suggested that the appearance of this second peak, termed peak ...

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In-vitro antifungal activity of liposomal nystatin in comparison with nystatin, amphotericin B cholesteryl sulphate, liposomal amphotericin B, amphotericin B lipid complex, amphotericin B desoxycholate, fluconazole and itraconazole

Cited by 78 publications

References 5 publications

Uptake ofAspergillus fumigatusConidia by Phagocytic and Nonphagocytic Cells In Vitro: Quantitation Using Strains Expressing Green Fluorescent Protein

Uptake ofAspergillus fumigatusConidia by Phagocytic and Nonphagocytic Cells In Vitro: Quantitation Using Strains Expressing Green Fluorescent Protein

Investigation on Processing Variables for the Preparation of Fluconazole-Loaded Ethyl Cellulose Microspheres by Modified Multiple Emulsion Technique

Differential Antifungal Activity of Isomeric Forms of Nystatin

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