Amphotericin B molecular organization as an essential factor to improve activity/toxicity ratio in the treatment of visceral leishmaniasis.

Abstract:

:An in vivo study has been performed in order to determine the influence of amphotericin B (AMB) molecular organization on the toxicity and activity of this drug in the treatment of experimental visceral leishmaniasis. Three formulations with similar composition but different drug molecular self-association in aqueous media were prepared. Acute toxicity was evaluated by injecting them in healthy hamsters. Sub-acute toxicity and efficacy were studied administering them to animals previously infected with Leishmania infantum. The preparation with drug molecules completely dissolved into monomers (formulation "C") and produced the highest acute toxicity. The formulation whose AMB molecules were disposed as non-water-soluble multi-aggregates (formulation "B") proved to provide the lowest acute toxicity. This formula also showed an improved activity, mainly in the liver, if compared with the third tested formulation containing AMB molecules disposed as smaller dimerical "water-soluble" aggregates (formulation "A"). As a conclusion, molecular aggregation in biological media should be an important factor to consider when researching or optimizing medicines containing AMB. The liberation of molecules as large dispersed non-water-soluble multi-aggregates seems to improve the narrow therapeutic margin attached to the use of this drug.

journal_name

J Drug Target

authors

Sánchez-Brunete JA,Dea MA,Rama S,Bolás F,Alunda JM,Torrado-Santiago S,Torrado JJ

doi

10.1080/10611860400006596

keywords:

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

453-60

issue

7

eissn

1061-186X

issn

1029-2330

pii

NKCNC4UXLNC1T4GL

journal_volume

12

pub_type

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