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. 1997 Apr;41(4):752–756. doi: 10.1128/aac.41.4.752

Activity of liposomal amphotericin B against experimental cutaneous leishmaniasis.

V Yardley 1, S L Croft 1
PMCID: PMC163788  PMID: 9087483

Abstract

The polyene antibiotic amphotericin B is currently a second-line treatment for visceral leishmaniasis (VL) and mucocutaneous leishmaniasis. Lipid-amphotericin B formulations with lower toxicity than the parent drug that were developed for the treatment of systemic mycoses have proved to be an effective treatment for VL, especially AmBisome, a small unilamellar negatively charged liposome. In vitro, free amphotericin B was three to six times more active than the liposomal formulation AmBisome against both Leishmania major promastigotes in culture and amastigotes in murine macrophages. In a BALB/c L. major model of cutaneous infection, liposomal amphotericin B administered once a day on six alternate days by the intravenous route produced a dose-response effect between 6.25 and 50 mg/kg. Liposomal amphotericin B administered subcutaneously close to a lesion had no significant activity. Free drug was ineffective at nontoxic doses. The results suggest that liposomal amphotericin B may be useful in the treatment of cutaneous leishmaniasis.

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Selected References

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  1. Aebischer T., Moody S. F., Handman E. Persistence of virulent Leishmania major in murine cutaneous leishmaniasis: a possible hazard for the host. Infect Immun. 1993 Jan;61(1):220–226. doi: 10.1128/iai.61.1.220-226.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allen T. M., Hansen C. B., Guo L. S. Subcutaneous administration of liposomes: a comparison with the intravenous and intraperitoneal routes of injection. Biochim Biophys Acta. 1993 Jul 25;1150(1):9–16. doi: 10.1016/0005-2736(93)90115-g. [DOI] [PubMed] [Google Scholar]
  3. Berman J. D., Hanson W. L., Chapman W. L., Alving C. R., Lopez-Berestein G. Antileishmanial activity of liposome-encapsulated amphotericin B in hamsters and monkeys. Antimicrob Agents Chemother. 1986 Dec;30(6):847–851. doi: 10.1128/aac.30.6.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bosque F., Moufqia J., Belkaid Y., Colle J. H., Leclercq V., Lebastard M., Milon G. Parasite-host relationships: in-situ study of Leishmania spp. in resistant and susceptible mice. Ann Trop Med Parasitol. 1995 Dec;89 (Suppl 1):19–22. doi: 10.1080/00034983.1995.11813010. [DOI] [PubMed] [Google Scholar]
  5. Croft S. L., Davidson R. N., Thornton E. A. Liposomal amphotericin B in the treatment of visceral leishmaniasis. J Antimicrob Chemother. 1991 Oct;28 (Suppl B):111–118. doi: 10.1093/jac/28.suppl_b.111. [DOI] [PubMed] [Google Scholar]
  6. Davidson R. N., Di Martino L., Gradoni L., Giacchino R., Russo R., Gaeta G. B., Pempinello R., Scott S., Raimondi F., Cascio A. Liposomal amphotericin B (AmBisome) in Mediterranean visceral leishmaniasis: a multi-centre trial. Q J Med. 1994 Feb;87(2):75–81. [PubMed] [Google Scholar]
  7. Davidson R. N., Russo R. Relapse of visceral leishmaniasis in patients who were coinfected with human immunodeficiency virus and who received treatment with liposomal amphotericin B. Clin Infect Dis. 1994 Sep;19(3):560–560. doi: 10.1093/clinids/19.3.560. [DOI] [PubMed] [Google Scholar]
  8. Dietze R., Fagundes S. M., Brito E. F., Milan E. P., Feitosa T. F., Suassuna F. A., Fonschiffrey G., Ksionski G., Dember J. Treatment of kala-azar in Brazil with Amphocil (amphotericin B cholesterol dispersion) for 5 days. Trans R Soc Trop Med Hyg. 1995 May-Jun;89(3):309–311. doi: 10.1016/0035-9203(95)90557-x. [DOI] [PubMed] [Google Scholar]
  9. Dietze R., Milan E. P., Berman J. D., Grogl M., Falqueto A., Feitosa T. F., Luz K. G., Suassuna F. A., Marinho L. A., Ksionski G. Treatment of Brazilian kala-azar with a short course of amphocil (amphotericin B cholesterol dispersion). Clin Infect Dis. 1993 Dec;17(6):981–986. doi: 10.1093/clinids/17.6.981. [DOI] [PubMed] [Google Scholar]
  10. Edmonds L. C., Davidson L., Bertino J. S. Effect of variation in infusion time and macrophage blockade on organ uptake of amphotericin B-deoxycholate. J Antimicrob Chemother. 1991 Dec;28(6):919–924. doi: 10.1093/jac/28.6.919. [DOI] [PubMed] [Google Scholar]
  11. ElHassan A. M., Gaafar A., Theander T. G. Antigen-presenting cells in human cutaneous leishmaniasis due to Leishmania major. Clin Exp Immunol. 1995 Mar;99(3):445–453. doi: 10.1111/j.1365-2249.1995.tb05571.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gradoni L., Bryceson A., Desjeux P. Treatment of Mediterranean visceral leishmaniasis. Bull World Health Organ. 1995;73(2):191–197. [PMC free article] [PubMed] [Google Scholar]
  13. Gradoni L., Davidson R. N., Orsini S., Betto P., Giambenedetti M. Activity of liposomal amphotericin B (AmBisome) against Leishmania infantum and tissue distribution in mice. J Drug Target. 1993;1(4):311–316. doi: 10.3109/10611869308996089. [DOI] [PubMed] [Google Scholar]
  14. Gregoriadis G. Overview of liposomes. J Antimicrob Chemother. 1991 Oct;28 (Suppl B):39–48. doi: 10.1093/jac/28.suppl_b.39. [DOI] [PubMed] [Google Scholar]
  15. Janknegt R., de Marie S., Bakker-Woudenberg I. A., Crommelin D. J. Liposomal and lipid formulations of amphotericin B. Clinical pharmacokinetics. Clin Pharmacokinet. 1992 Oct;23(4):279–291. doi: 10.2165/00003088-199223040-00004. [DOI] [PubMed] [Google Scholar]
  16. Jha T. K., Giri Y. N., Singh T. K., Jha S. Use of amphotericin B in drug-resistant cases of visceral leishmaniasis in north Bihar, India. Am J Trop Med Hyg. 1995 Jun;52(6):536–538. doi: 10.4269/ajtmh.1995.52.536. [DOI] [PubMed] [Google Scholar]
  17. Khoo S. H., Bond J., Denning D. W. Administering amphotericin B--a practical approach. J Antimicrob Chemother. 1994 Feb;33(2):203–213. doi: 10.1093/jac/33.2.203. [DOI] [PubMed] [Google Scholar]
  18. Lasic D. D., Papahadjopoulos D. Liposomes revisited. Science. 1995 Mar 3;267(5202):1275–1276. doi: 10.1126/science.7871422. [DOI] [PubMed] [Google Scholar]
  19. Legrand P., Vertut-Doi A., Bolard J. Comparative internalization and recycling of different amphotericin B formulations by a macrophage-like cell line. J Antimicrob Chemother. 1996 Mar;37(3):519–533. doi: 10.1093/jac/37.3.519. [DOI] [PubMed] [Google Scholar]
  20. Locksley R. M., Louis J. A. Immunology of leishmaniasis. Curr Opin Immunol. 1992 Aug;4(4):413–418. doi: 10.1016/s0952-7915(06)80032-4. [DOI] [PubMed] [Google Scholar]
  21. Milano S., Arcoleo F., Dieli M., D'Agostino R., De Nucci G., D'Agostino P., Cillari E. Ex vivo evidence for PGE2 and LTB4 involvement in cutaneous leishmaniasis: relation with infection status and cytokine production. Parasitology. 1996 Jan;112(Pt 1):13–19. doi: 10.1017/s0031182000065033. [DOI] [PubMed] [Google Scholar]
  22. Mirkovich A. M., Galelli A., Allison A. C., Modabber F. Z. Increased myelopoiesis during Leishmania major infection in mice: generation of 'safe targets', a possible way to evade the effector immune mechanism. Clin Exp Immunol. 1986 Apr;64(1):1–7. [PMC free article] [PubMed] [Google Scholar]
  23. Murray H. W. Blood monocytes: differing effector role in experimental visceral versus cutaneous leishmaniasis. Parasitol Today. 1994 Jun;10(6):220–223. doi: 10.1016/0169-4758(94)90117-1. [DOI] [PubMed] [Google Scholar]
  24. New R. R., Chance M. L., Heath S. Antileishmanial activity of amphotericin and other antifungal agents entrapped in liposomes. J Antimicrob Chemother. 1981 Nov;8(5):371–381. doi: 10.1093/jac/8.5.371. [DOI] [PubMed] [Google Scholar]
  25. Panosian C. B., Barza M., Szoka F., Wyler D. J. Treatment of experimental cutaneous leishmaniasis with liposome-intercalated amphotericin B. Antimicrob Agents Chemother. 1984 May;25(5):655–656. doi: 10.1128/aac.25.5.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pitt A., Mayorga L. S., Schwartz A. L., Stahl P. D. Transport of phagosomal components to an endosomal compartment. J Biol Chem. 1992 Jan 5;267(1):126–132. [PubMed] [Google Scholar]
  27. Proffitt R. T., Satorius A., Chiang S. M., Sullivan L., Adler-Moore J. P. Pharmacology and toxicology of a liposomal formulation of amphotericin B (AmBisome) in rodents. J Antimicrob Chemother. 1991 Oct;28 (Suppl B):49–61. doi: 10.1093/jac/28.suppl_b.49. [DOI] [PubMed] [Google Scholar]
  28. Saha A. K., Mukherjee T., Bhaduri A. Mechanism of action of amphotericin B on Leishmania donovani promastigotes. Mol Biochem Parasitol. 1986 Jun;19(3):195–200. doi: 10.1016/0166-6851(86)90001-0. [DOI] [PubMed] [Google Scholar]
  29. Seaman J., Boer C., Wilkinson R., de Jong J., de Wilde E., Sondorp E., Davidson R. Liposomal amphotericin B (AmBisome) in the treatment of complicated kala-azar under field conditions. Clin Infect Dis. 1995 Jul;21(1):188–193. doi: 10.1093/clinids/21.1.188. [DOI] [PubMed] [Google Scholar]
  30. Thakur C. P., Pandey A. K., Sinha G. P., Roy S., Behbehani K., Olliaro P. Comparison of three treatment regimens with liposomal amphotericin B (AmBisome) for visceral leishmaniasis in India: a randomized dose-finding study. Trans R Soc Trop Med Hyg. 1996 May-Jun;90(3):319–322. doi: 10.1016/s0035-9203(96)90271-0. [DOI] [PubMed] [Google Scholar]
  31. Torre-Cisneros J., Prada J. L., Villanueva J. L., Valverde F., Sánchez-Guijó P. Successful treatment of antimony-resistant cutaneous leishmaniasis with liposomal amphotericin B. Clin Infect Dis. 1994 Jun;18(6):1024–1025. doi: 10.1093/clinids/18.6.1024. [DOI] [PubMed] [Google Scholar]
  32. Vertut-Doï A., Ohnishi S. I., Bolard J. The endocytic process in CHO cells, a toxic pathway of the polyene antibiotic amphotericin B. Antimicrob Agents Chemother. 1994 Oct;38(10):2373–2379. doi: 10.1128/aac.38.10.2373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wasan K. M., Lopez-Berestein G. The interaction of liposomal amphotericin B and serum lipoproteins within the biological milieu. J Drug Target. 1994;2(5):373–380. doi: 10.3109/10611869408996812. [DOI] [PubMed] [Google Scholar]
  34. Wasan K. M., Morton R. E., Rosenblum M. G., Lopez-Berestein G. Decreased toxicity of liposomal amphotericin B due to association of amphotericin B with high-density lipoproteins: role of lipid transfer protein. J Pharm Sci. 1994 Jul;83(7):1006–1010. doi: 10.1002/jps.2600830716. [DOI] [PubMed] [Google Scholar]
  35. Wu N. Z., Da D., Rudoll T. L., Needham D., Whorton A. R., Dewhirst M. W. Increased microvascular permeability contributes to preferential accumulation of Stealth liposomes in tumor tissue. Cancer Res. 1993 Aug 15;53(16):3765–3770. [PubMed] [Google Scholar]
  36. de Marie S., Janknegt R., Bakker-Woudenberg I. A. Clinical use of liposomal and lipid-complexed amphotericin B. J Antimicrob Chemother. 1994 May;33(5):907–916. doi: 10.1093/jac/33.5.907. [DOI] [PubMed] [Google Scholar]
  37. van Etten E. W., Otte-Lambillion M., van Vianen W., ten Kate M. T., Bakker-Woudenberg A. J. Biodistribution of liposomal amphotericin B (AmBisome) and amphotericin B-desoxycholate (Fungizone) in uninfected immunocompetent mice and leucopenic mice infected with Candida albicans. J Antimicrob Chemother. 1995 Apr;35(4):509–519. doi: 10.1093/jac/35.4.509. [DOI] [PubMed] [Google Scholar]

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