Efficacies of vesicular and free sodium stibogluconate formulations against clinical isolates of leishmania donovani

K.C. Carter, A. Mullen, S. Sundar, R.T. Kenney

Research output: Contribution to journalArticle

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Abstract

In this study, the in vitro and in vivo efficacies of free sodium stibogluconate (SSG) and a nonionic surfactant vesicular formulation of SSG (SSG-NIV) against a laboratory strain ofLeishmania donovani (MHOM/ET/67:LV82) and different clinical isolates of L. donovani were determined. Treatment with SSG-NIV was more effective against intramacrophage amastigotes than treatment with SSG. In vivo murine studies showed that there was interstrain variability in the infectivity of the different L. donovani strains, with two of the strains (20001 and 20003) giving low parasite burdens. In addition, interstrain variability in the antileishmanial efficacy of SSG in a single dose containing 300 mg of Sb(V)/kg of body weight was observed. This dose of free drug either caused a >97% reduction in liver parasite burdens or had no significant effect on parasite burdens compared with the result with the respective control. In some instances, treatment with this free SSG dose also caused a significant reduction in spleen (strain 20006) or bone marrow (strains 20001 and 20009) parasite burdens. Treatment with SSG-NIV was more effective than that with SSG against all of the strains tested. In SSG-responsive strains, the reduction in liver parasite burdens by SSG-NIV treatment was similar to that caused by free SSG. In SSG-nonresponsive strains, SSG-NIV treatment caused at least a 95% reduction in liver parasite burdens. Overall, these results indicate that the use of a vesicular formulation of SSG is likely to increase its clinical efficacy against visceral leishmaniasis.
LanguageEnglish
Pages355-359
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume45
Issue number12
DOIs
Publication statusPublished - Dec 2001

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Antimony Sodium Gluconate
Leishmania donovani
Parasites
Liver

Keywords

  • Leishmania donovani
  • visceral leishmaniasis
  • liver parasite burdens

Cite this

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abstract = "In this study, the in vitro and in vivo efficacies of free sodium stibogluconate (SSG) and a nonionic surfactant vesicular formulation of SSG (SSG-NIV) against a laboratory strain ofLeishmania donovani (MHOM/ET/67:LV82) and different clinical isolates of L. donovani were determined. Treatment with SSG-NIV was more effective against intramacrophage amastigotes than treatment with SSG. In vivo murine studies showed that there was interstrain variability in the infectivity of the different L. donovani strains, with two of the strains (20001 and 20003) giving low parasite burdens. In addition, interstrain variability in the antileishmanial efficacy of SSG in a single dose containing 300 mg of Sb(V)/kg of body weight was observed. This dose of free drug either caused a >97{\%} reduction in liver parasite burdens or had no significant effect on parasite burdens compared with the result with the respective control. In some instances, treatment with this free SSG dose also caused a significant reduction in spleen (strain 20006) or bone marrow (strains 20001 and 20009) parasite burdens. Treatment with SSG-NIV was more effective than that with SSG against all of the strains tested. In SSG-responsive strains, the reduction in liver parasite burdens by SSG-NIV treatment was similar to that caused by free SSG. In SSG-nonresponsive strains, SSG-NIV treatment caused at least a 95{\%} reduction in liver parasite burdens. Overall, these results indicate that the use of a vesicular formulation of SSG is likely to increase its clinical efficacy against visceral leishmaniasis.",
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Efficacies of vesicular and free sodium stibogluconate formulations against clinical isolates of leishmania donovani. / Carter, K.C.; Mullen, A.; Sundar, S.; Kenney, R.T.

In: Antimicrobial Agents and Chemotherapy, Vol. 45, No. 12, 12.2001, p. 355-359.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Efficacies of vesicular and free sodium stibogluconate formulations against clinical isolates of leishmania donovani

AU - Carter, K.C.

AU - Mullen, A.

AU - Sundar, S.

AU - Kenney, R.T.

PY - 2001/12

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N2 - In this study, the in vitro and in vivo efficacies of free sodium stibogluconate (SSG) and a nonionic surfactant vesicular formulation of SSG (SSG-NIV) against a laboratory strain ofLeishmania donovani (MHOM/ET/67:LV82) and different clinical isolates of L. donovani were determined. Treatment with SSG-NIV was more effective against intramacrophage amastigotes than treatment with SSG. In vivo murine studies showed that there was interstrain variability in the infectivity of the different L. donovani strains, with two of the strains (20001 and 20003) giving low parasite burdens. In addition, interstrain variability in the antileishmanial efficacy of SSG in a single dose containing 300 mg of Sb(V)/kg of body weight was observed. This dose of free drug either caused a >97% reduction in liver parasite burdens or had no significant effect on parasite burdens compared with the result with the respective control. In some instances, treatment with this free SSG dose also caused a significant reduction in spleen (strain 20006) or bone marrow (strains 20001 and 20009) parasite burdens. Treatment with SSG-NIV was more effective than that with SSG against all of the strains tested. In SSG-responsive strains, the reduction in liver parasite burdens by SSG-NIV treatment was similar to that caused by free SSG. In SSG-nonresponsive strains, SSG-NIV treatment caused at least a 95% reduction in liver parasite burdens. Overall, these results indicate that the use of a vesicular formulation of SSG is likely to increase its clinical efficacy against visceral leishmaniasis.

AB - In this study, the in vitro and in vivo efficacies of free sodium stibogluconate (SSG) and a nonionic surfactant vesicular formulation of SSG (SSG-NIV) against a laboratory strain ofLeishmania donovani (MHOM/ET/67:LV82) and different clinical isolates of L. donovani were determined. Treatment with SSG-NIV was more effective against intramacrophage amastigotes than treatment with SSG. In vivo murine studies showed that there was interstrain variability in the infectivity of the different L. donovani strains, with two of the strains (20001 and 20003) giving low parasite burdens. In addition, interstrain variability in the antileishmanial efficacy of SSG in a single dose containing 300 mg of Sb(V)/kg of body weight was observed. This dose of free drug either caused a >97% reduction in liver parasite burdens or had no significant effect on parasite burdens compared with the result with the respective control. In some instances, treatment with this free SSG dose also caused a significant reduction in spleen (strain 20006) or bone marrow (strains 20001 and 20009) parasite burdens. Treatment with SSG-NIV was more effective than that with SSG against all of the strains tested. In SSG-responsive strains, the reduction in liver parasite burdens by SSG-NIV treatment was similar to that caused by free SSG. In SSG-nonresponsive strains, SSG-NIV treatment caused at least a 95% reduction in liver parasite burdens. Overall, these results indicate that the use of a vesicular formulation of SSG is likely to increase its clinical efficacy against visceral leishmaniasis.

KW - Leishmania donovani

KW - visceral leishmaniasis

KW - liver parasite burdens

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DO - 10.1128/AAC.45.12.3555-3559.2001

M3 - Article

VL - 45

SP - 355

EP - 359

JO - Antimicrobial Agents and Chemotherapy

T2 - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 12

ER -