Treatment of Experimental Visceral Leishmaniasis with Amphotericin B in Stable Albumin Microspheres

Abstract

Hydrophilic albumin microspheres are proposed as a new delivery system for amphotericin B (AMB; AMB microspheres). The acute toxicity of AMB microspheres was lower than that of the AMB-deoxycholate (AMBDoc) reference formulation in hamsters. Lethal doses in healthy and infected animals were improved at least eight times. Intravenous bolus administration of doses of AMB microspheres up to 40 mg/kg of body weight did not produce acute symptoms of toxicity. The efficacy of this new formulation was tested against Leishmania infantum-infected hamsters at doses of 2, 10, 20, and 40 mg/kg. With the 2-mg/kg dose, the activity of AMB, as assessed through the parasite load reductions in the liver and spleen and the evolution of antibody levels, was also improved (P < 0.05) by use of the AMB microsphere system. At the higher doses of 10, 20, and 40 mg/kg, reductions in parasite levels of more than 99% were achieved in the liver and spleen after the administration of AMB microspheres. A pharmacokinetic study was performed to study the serum, liver, and spleen AMB concentrations after administration of AMB microspheres and the reference formulation. Interestingly, a significant accumulation of AMB in the spleen and liver was observed after AMB microsphere administration. Our results suggest that this new formulation is a promising alternative to the conventional AMB-Doc formulation for the treatment of visceral leishmaniasis.

Essential oil from leaves of Lantana camara: a potential source of medicine against leishmaniasis

“…According to Sanchez-Brunete et al (2004), Amphotericin B caused behavior alterations and death in hamsters that received it at doses that ranged from 10 to 20 mg/mL per kg of body weight along a 48 h period. Comparing the doses used in this study to those used in the mentioned one, despite different species, it is possible to suggest a remarkably higher toxicity of Amphotericin B than EOLC, which revealed significant inhibitory activity of promastigote proliferation in vitro.…”

HPLC assay for determination of amphotericin B in biological samples

“…As an example, the proposed HPLC method was applied to determine the plasma concentration-time profiles of AB following intravenous bolus administration of a new AB formulation, consisting of albumin microspheres containing AB (AB-Mic) elaborated by a spray-drying process (Sánchez-Brunete et al, 2004), in dog and mice. AB-Mic was prepared by dispersing of AMB in 5 mL of a water solution formed by sodium deoxycholate, dibasic sodium phosphate and monobasic sodium phosphate.…”

Uptake of Biodegradable Gel-Assisted LBL Nanomatrix by Leishmania donovani-Infected Macrophages

“…The most prevalent treatment consists of the administration of antimonials but there is growing evidence that the rate of response to the antimonials are declining due to the emergence of resistance and frequent relapses (1). Cytotoxic drugs like methotrexate and doxorubicin hydrochloride (DOX) are reported to be highly effective against VL but their therapeutic value, however, is strongly limited by cumulative dose-dependent cardiotoxicity (2)(3)(4). Herein, we introduce assembled gel-assisted nanomatrix loaded with DOX (layer-by-layer (LBL)-DOX) based on novel LBL technology for antileishmanial therapy to overcome the obstacles of resistance and toxicity as represented in Scheme 1.…”