Role of Macrophages in the Candidacidal Activity of Liposomal Amphotericin B

Mehta, R.; Poddar, Sourav; Kalidas, Mamta; Gómez-Flores, Ricardo; Dulski, Kim M.

doi:10.1093/infdis/175.1.214

Cited by 13 publications

(9 citation statements)

References 14 publications

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“…administration as well as administration of higher doses, enhancing therapeutic efficacy as observed in our studies with MAC (15,20). Studies with some other antimicrobials have shown similar results (4,16,19,22,23).…”

Section: Discussionsupporting

confidence: 88%

Effective Treatment of Acute and Chronic Murine Tuberculosis with Liposome-Encapsulated Clofazimine

Adams

Sinha

Franzblau

et al. 1999

Antimicrob Agents Chemother

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The therapeutic efficacy of liposomal clofazimine (L-CLF) was studied in mice infected with Mycobacterium tuberculosisErdman. Groups of mice were treated with either free clofazimine (F-CLF), L-CLF, or empty liposomes twice a week for five treatments beginning on day 1 (acute), day 21 (established), or day 90 (chronic) postinfection. One day after the last treatment, the numbers of CFU ofM. tuberculosis in the spleen, liver, and lungs were determined. F-CLF at the maximum tolerated dose of 5 mg/kg of body weight was ineffective; however, 10-fold-higher doses of L-CLF demonstrated a dose response with significant CFU reduction in all tissues without any toxic effects. In acutely infected mice, 50 mg of L-CLF/kg reduced CFU 2 to 3 log units in all three organs. In established or chronic infection, treated mice showed no detectable CFU in the spleen or liver and 1- to 2-log-unit reduction in the lungs. A second series of L-CLF treatments cleared M. tuberculosisin all three tissues. L-CLF appears to be bactericidal in the liver and spleen, which remained negative for M. tuberculosis growth for 2 months. Thus, L-CLF could be useful in the treatment of tuberculosis.

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Section: Discussionsupporting

confidence: 88%

Effective Treatment of Acute and Chronic Murine Tuberculosis with Liposome-Encapsulated Clofazimine

Adams

Sinha

Franzblau

et al. 1999

Antimicrob Agents Chemother

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“…Conventional preparations of AmB enhance macrophage activity [34][35][36][37] and thus increase activation of NK cells and T lymphocytes [10,18,19,38] via the elaboration of regulatory cytokines such as interleukin (IL)-12 [10,38,39]. The immunomodulation of macrophage activity has been suggested to be due to the auto-oxidation of AmB in conjunction with the formation of free radicals [33].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, free AmB is released at lower concentrations by liposomal carriers, which is above the MIC for sensitive fungi but not sufficiently high to induce mammalian cell toxicity. It has been argued that, rather than having a direct effect on macrophages, L-AmB's success in up-regulating macrophage-mediated killing of fungal cells is due to the increased uptake, transport, and delivery of L-AmB directly to infected areas [34,35,42]. Yet evidence from animal models suggests that L-AmB might stabilize macrophage membrane composition as well as oxidative pathways [36,51,58,59].…”

Section: Discussionmentioning

confidence: 99%

Liposomal Amphotericin B and Amphotericin B–Deoxycholate Show Different Immunoregulatory Effects on Human Peripheral Blood Mononuclear Cells

Reyes¹,

Cardona²,

Prieto³

et al. 2000

J INFECT DIS

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Conventional preparations of amphotericin B (AmB) at established therapeutic doses are known to increase nonspecific immune responses. It remains to be established whether higher doses of the less toxic liposomal preparation of AmB maintains a beneficial effect on the immune response to fungal infections. Examination of the effect of treatment of human peripheral blood mononuclear cells from healthy subjects with various doses of both liposomal AmB (L-AmB) and deoxycholate AmB (d-AmB) on proliferation, cell viability, and percentage of apoptosis demonstrated that, although both L-AmB and d-AmB at low doses significantly increased nonspecific proliferative responses, L-AmB, but not d-AmB, treatment maintained this beneficial effect at higher doses. High doses of d-AmB, but not L-AmB, resulted in significantly decreased cell viability and increased apoptosis. This study provides further evidence in healthy human subjects for choosing L-AmB over conventional preparations in the clinical treatment of fungal infections requiring systemic high-dose treatment with AmB.

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“…Mehta et al (1997) conducted a study to investigate the role of macrophages in candidacidal activity of L-AmB. The results suggested that the improved candidacidal activity of L-AmB was possibly not due to activation of the macrophages.…”

Section: Role Of Lipid Formulationsmentioning

confidence: 99%

Optimizing efficacy of amphotericin B through nanomodification

Vyas¹,

Gupta²

2006

International Journal of Nanomedicine

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Fungal infections and leishmaniasis are an important cause of morbidity and mortality in immunocompromised patients. The macrolide polyene antibiotic amphotericin B (AmB) has long been recognized as a powerful fungicidal and leishmanicidal drug. A conventional intravenous dosage form of AmB, AmB-deoxycholate (Fungizone or D-AmB), is the most effective clinically available for treating fungal and parasitic (leishmaniasis) infections. However, the clinical effi cacy of AmB is limited by its adverse effects mainly nephrotoxicity. Efforts to lower the toxicity are based on synthesis of AmB analogues such as AmB esters or preparation of AmB-lipid associations in the forms of liposomal AmB (L-AmB or AmBisome), AmB lipid complex (Abelcet or ABLC), AmB colloidal dispersion (Amphocil or ABCD), and intralipid AmB. These newer formulations are substantially more expensive, but allow patients to receive higher doses for longer periods of time with decreased renal toxicity than conventional AmB. Modifi cations of liposomal surface in order to avoid RES uptake, thus increased targetability has been attempted. Emulsomes and other nanoparticles are special carrier systems for intracellular localization in macrophage rich organs like liver and spleen. Injectable nano-carriers have important potential applications as in site-specifi c drug delivery.

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Role of Macrophages in the Candidacidal Activity of Liposomal Amphotericin B

Cited by 13 publications

References 14 publications

Effective Treatment of Acute and Chronic Murine Tuberculosis with Liposome-Encapsulated Clofazimine

Effective Treatment of Acute and Chronic Murine Tuberculosis with Liposome-Encapsulated Clofazimine

Liposomal Amphotericin B and Amphotericin B–Deoxycholate Show Different Immunoregulatory Effects on Human Peripheral Blood Mononuclear Cells

Optimizing efficacy of amphotericin B through nanomodification

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