INVESTIGADORES
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artículos
Título:
Benznidazole vs benznidazole in multilamellar liposomes: How different they interect with blood components?
Autor/es:
MORILLA, MARIA JOSE, PRIETO, MARIA JIMENA AND ROMERO, EDER LILIA.
Revista:
MEMóRIAS DO INSTITUTO OSWALDO CRUZ.
Referencias:
Año: 2005 vol. 100 p. 213 - 219
ISSN:
0074-0276
Resumen:
In spite of its widespread use, benznidazolefs (BNZ) toxicity and low efficacy remains as major drawbacks that
impair successful treatments against Chagas disease. Previously, attempting to increase the selectivity and reduce
its toxicity on infected tissues, multilamellar liposomes (MLV) composed of hydrogenated soybean phosphatidylcholine
(HSPC): distearoyl-phosphatidylglycerol (DSPG): cholesterol (CHOL) 2:1:2 mol:mol loaded with BNZ
(MLV-BNZ) were designed. In this work we compared different properties of MLV-BNZ with those of BNZ. Opposite
to other hydrophobic drugs, the results indicated that slight changes of BNZLs association degree to proteins and
lipoproteins should not modify the percentage of unbound drug available to exert pharmacological action. On the
other hand, when loaded in MLV, BNZ reduced its association to plasma proteins in 45% and became refractory to
the sinking effect of blood, dropping 4.5 folds. Additionally, when loaded in MLV, BNZ had higher volume distribution
(160 } 20 vs 102 } 15 ml/kg) and total clearance (35.23 } 2.3 vs 21.9 } 1.4 ml/h.kg), and lower concentrationtime
curve (7.23 } 0.2 vs 9.16 } 0.5 Êg.h/ml) than BNZ. Hence, these studies showed that for MLV-BNZ, the amount
of BNZ can be substantially increased, from 25 to 70%, being this formulation more rapidly cleared from circulation
than free drug; also due to the lower interaction with blood components, lower side effects can be expected.