Comparison of the efficacies of various formulations of amphotericin B against murine visceral leishmaniasis

Abstract

The antileishmanial efficacies of four proprietary amphotericin B (AmB) formulations (Fungizone, AmBisome, Abelcet, and Amphocil) and an experimental nonionic surfactant vesicle (NIV) formulation were compared in a murine model of acute visceral leishmaniasis. By a multiple-dosing regimen, groups of Leishmania donovani-infected BALB/c mice were treated (2.5 mg of AmB per kg of body weight) on days 7 to 11 postinfection with one of the AmB formulations, and parasite burdens were determined on day 18 postinfection. All of the formulations caused significant suppression parasite burdens in spleens (P < 0.01 to 0.0005) and livers (P < 0.0005) compared with those in the spleens and livers of the controls. In addition, a significant suppression of parasite burdens in bone marrow (P < 0.0005) compared to the burdens in the bone marrow of the controls was obtained for all the formulations except Abelcet, which was inactive at this site. On the basis of their overall efficacies (activity against liver, spleen, and bone marrow parasites), the formulations could be ranked as follows: Amphocil = AmBisome > AmB-NIV > Abelcet > Fungizone. On the basis of spectrophotometric measurements, AmB was shown to exist in a predominantly aggregated state in all of the formulations. Although incubation in 50% serum altered the degree of aggregation, the AmB remained predominantly aggregated, indicating that the AMB-lipid complex in all of the formulations was physically stable. The results of the study showed that antiparasitic efficacy is associated positively with the degree of AmB aggregation in the presence of serum.

Amphotericin B-Gum Arabic Conjugates: Synthesis, Toxicity, Bioavailability, and Activities Against Leishmania and Fungi

“…It is also reported to be toxic to liver and heart (26,28). Therefore, the internal organs; brain, kidney, liver, heart, spleen and muscles of mice that received maximum tolerable dosage was observed for morphological changes.…”

Therapeutic Vaccination With Recombinant Adenovirus Reduces Splenic Parasite Burden in Experimental Visceral Leishmaniasis

“…Although it is unlikely that a therapeutic vaccine would be used alone [11], we set our criterion for success as inhibition of parasite growth of 50%. This level of response equates favorably to that seen following single dose therapy using 4 mg/kg Ambisome [26] or administration of sodium stibogluconate [27], although better responses are achievable with longer chemotherapy [26, 28]. Second, for clinical practicality, we aimed for efficacy using a single vaccination.…”

In Vitro Antileishmanial Activity of Amphotericin B Loaded in Poly(ε-Caprolactone) Nanospheres

“…The decrease in activity as compared with free AmB and also the notable differences found among them (Yardley and Croft, 2000) was suggested as probably related to differences in their uptake and availability of the drug by the macrophages (Legrand et al, 1996). These effects were closely related to the strong interaction between the drug and the carrier compounds, that impaired the access of AmB inside the macrophages and the ability of the drug to interact with ergosterol in the parasite membrane (Müllen et al, 1997;Yardley and Croft, 2000). In our formulations, AmB was mainly adsorbed onto the carrier surface and desorption happens upon high dilution (concentrations below 1 mg/ml) (Espuelas et al, 1997;.…”