Activity of Liposomal Amphotericin B with Prolonged Circulation in Blood versus Those of AmBisome and Fungizone against Intracellular Candida albicans in Murine Peritoneal Macrophages

Abstract

Activity against intracellular Candida albicans was assessed in C. albicans-infected murine peritoneal macrophages exposed to long-circulating pegylated amphotericin B liposomes (PEG-AMB-LIP), AmBisome, or Fungizone. The level of antifungal activity of Fungizone is much higher than that of AmBisome or PEG-AMB-LIP, while PEG-AMB-LIP and AmBisome show equivalent activity levels. Previous exposure of uninfected macrophages to PEG-AMB-LIP or AmBisome is advantageous for intracellular antifungal activity.

Combating Fungal Infections

“…Saponins are natural detergents that are effective antimicrobial, cholesterol-lowering anticancer compounds. In comparison to L-AmB, it conferred a significantly prolonged blood residence time, and displayed dose-independent pharmacokinetics over a large range of dosages (van Etten et al 1998b). The results showed that there were significantly fewer proven breakthrough fungal infections in the AmBisome™ treatment group.…”

“…These compounds chemically related to the triterpenoid group such as Walsh et al (1999) compared AmBisome™ 3 mg/kg/day with Fungizone 1 0.6 mg/kg/day. In a leukopenic mouse model of disseminated candidiasis, PEG L-AmB had enhanced antifungal efficacy as compared to the nonPEGylated product and L-AmB (AmBisome™) (van Etten et al 1995b(van Etten et al , 1998b. van Etten et al (1995b) reported that the therapeutic efficacy of liposomal AmB coated with PEG (PEG-L-AmB) was better than that of AmBisome™ against invasive candidiasis in neutropenic mice.…”

Toward an Optimized Treatment of Intracellular Bacterial Infections: Input of Nanoparticulate Drug Delivery Systems

“…Peritoneal macrophages Cephalothin Liposomes 1983 [102,103] Ampicillin Nanoparticles 1994 [104] 1994 [105] Chitosan 1996 [106] RAW 264.7, intestine 407 cells Ciprofloxacin Nanocapsules 2012 [107] Murine macrophage-like J774A.1 Gentamicin Liposomes 2013 [66] 1998 [65] Salmonella enterica Infected liver and spleen in a murine salmonellosis model Gentamicin Liposomes 2000 [108] J774A.1 macrophage cells Gentamicin Polymer complexes 2009 [109] Listeria monocytogenes Neutrophils Cloxacillin Liposomes 1986 [110] Human THP-1 cells, murine J 774 cells Gentamicin Nanoparticles 2010 [11] Peritoneal macrophages Ampicillin Liposomes 1988 [111] Nanoparticles 1992 [112] Escherichia coli Peritoneal macrophages Streptomycin Liposomes 1983 [113] Brucella abortus Mononuclear leukocytes Gentamicin Liposomes 1985 [114] Peritoneal macrophages 1985 [115] J 774 cells Nanoparticles 1996 [116] J 774 cells 2012 [117] THP-1 cells Micelles 2012 [118] Brucella melitensis THP-1 human monocytes Gentamicin Micro and nanoparticles 2006 [119] Candida albicans Murine peritoneal macrophages Amphotericin Liposomes 1998 [120] Chlamydia trachomatis and Chlamydia pneumoniae HEp2 cells Rifampin, azithromycin Nanoparticles 2011 [121] Toward an optimized treatment of intracellular bacterial infections Review higher with inhaled microparticles as compared with free drugs administered orally or by intracardiac injection.…”

Novel Drug Delivery Systems for Antifungal Compounds

“…In comparison to L-AmB, it conferred a significantly prolonged blood residence time, and displayed dose-independent pharmacokinetics over a large range of dosages (van Etten et al 1998b). In a leukopenic mouse model of disseminated candidiasis, PEG L-AmB had enhanced antifungal efficacy as compared to the nonPEGylated product and L-AmB (AmBisome™) (van Etten et al 1995b(van Etten et al , 1998b. In another study, immunoliposomes of PEG-L-AmB provided enhanced survival and tissue clearance in a murine model of pulmonary aspergillosis (Otsubo et al 1998).…”