Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1988 Jul;32(7):966–970. doi: 10.1128/aac.32.7.966

In vitro lysis of the bloodstream forms of Trypanosoma brucei gambiense by stearylamine-bearing liposomes.

H Tachibana 1, E Yoshihara 1, Y Kaneda 1, T Nakae 1
PMCID: PMC172326  PMID: 3056249

Abstract

Cytolytic activity of liposomes consisting of stearylamine and phosphatidylcholine (SA/PC-liposomes) was examined in vitro against the bloodstream forms of Trypanosoma brucei gambiense. More than 99% of the cells (2 X 10(6)/ml) were killed within 30 min by treatment with 15 mol% SA/PC-liposomes (100 microM total lipids). As few as 1.2 X 10(12) liposomes per ml (equivalent to 2 nM liposome) showed trypanocidal activity. Fluorescence microscopy of cells treated with the dansylated SA/PC-liposomes suggested that the liposomes bound to and accumulated on the cell surface, eventually damaging the plasma membrane. SA/PC-liposomes showed no significant hemolysis when incubated with human and mouse erythrocytes under conditions that killed greater than 99.9% of the T. b. gambiense trypomastigotes. Human leukocytes were also shown to be less susceptible to SA/PC-liposomes than T. b. gambiense. These results may point to a new direction in strategy for therapy of African trypanosomiasis.

Full text

PDF
967

Images in this article

968Image
on p.968

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alving C. R., Steck E. A., Chapman W. L., Jr, Waits V. B., Hendricks L. D., Swartz G. M., Jr, Hanson W. L. Liposomes in leishmaniasis: therapeutic effects of antimonial drugs, 8-aminoquinolines, and tetracycline. Life Sci. 1980 Jun 30;26(26):2231–2238. doi: 10.1016/0024-3205(80)90207-6. [DOI] [PubMed] [Google Scholar]
  2. Alving C. R., Steck E. A., Chapman W. L., Jr, Waits V. B., Hendricks L. D., Swartz G. M., Jr, Hanson W. L. Therapy of leishmaniasis: superior efficacies of liposome-encapsulated drugs. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2959–2963. doi: 10.1073/pnas.75.6.2959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Alving C. R., Steck E. A., Hanson W. L., Loizeaux P. S., Chapman W. L., Jr, Waits V. B. Improved therapy of experimental leishmaniasis by use of a liposome-encapsulated antimonial drug. Life Sci. 1978 Mar;22(12):1021–1026. doi: 10.1016/0024-3205(78)90270-9. [DOI] [PubMed] [Google Scholar]
  4. Alving C. R., Swartz G. M., Jr, Hendricks L. D., Chapman W. L., Jr, Waits V. B., Hanson W. L. Liposomes in leishmaniasis: effects of parasite virulence on treatment of experimental leishmaniasis in hamsters. Ann Trop Med Parasitol. 1984 Jun;78(3):279–286. doi: 10.1080/00034983.1984.11811817. [DOI] [PubMed] [Google Scholar]
  5. Black C. D., Watson G. J., Ward R. J. The use of Pentostam liposomes in the chemotherapy of experimental leishmaniasis. Trans R Soc Trop Med Hyg. 1977;71(6):550–552. doi: 10.1016/0035-9203(77)90155-9. [DOI] [PubMed] [Google Scholar]
  6. Chapman W. L., Jr, Hanson W. L., Alving C. R., Hendricks L. D. Antileishmanial activity of liposome-encapsulated meglumine antimonate in the dog. Am J Vet Res. 1984 May;45(5):1028–1030. [PubMed] [Google Scholar]
  7. De Carvalho T. U., Souto-Padróon T., De Souza W. Trypanosoma cruzi: surface charge and freeze-fracture of amastigotes. Exp Parasitol. 1985 Feb;59(1):12–23. doi: 10.1016/0014-4894(85)90052-9. [DOI] [PubMed] [Google Scholar]
  8. De Souza W., Arguello C., Martinez-Paloma A., Trissl D., Gonzáles-Robles A., Chiari E. Surface charge of trypanosoma cruzi. Binding of cationized ferritin and measurement of cellular electrophoretic mobility. J Protozool. 1977 Aug;24(3):411–415. doi: 10.1111/j.1550-7408.1977.tb04762.x. [DOI] [PubMed] [Google Scholar]
  9. Gutteridge W. E. Existing chemotherapy and its limitations. Br Med Bull. 1985 Apr;41(2):162–168. doi: 10.1093/oxfordjournals.bmb.a072044. [DOI] [PubMed] [Google Scholar]
  10. Lanham S. M., Godfrey D. G. Isolation of salivarian trypanosomes from man and other mammals using DEAE-cellulose. Exp Parasitol. 1970 Dec;28(3):521–534. doi: 10.1016/0014-4894(70)90120-7. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. New R. R., Chance M. L., Thomas S. C., Peters W. Antileishmanial activity of antimonials entrapped in liposomes. Nature. 1978 Mar 2;272(5648):55–56. doi: 10.1038/272055a0. [DOI] [PubMed] [Google Scholar]
  13. New R. R., Chance M. L. Treatment of experimental cutaneous leishmaniasis by liposome-entrapped Pentostam. Acta Trop. 1980 Sep;37(3):253–256. [PubMed] [Google Scholar]
  14. PHILLIPS H. J., TERRYBERRY J. E. Counting actively metabolizing tissue cultured cells. Exp Cell Res. 1957 Oct;13(2):341–347. doi: 10.1016/0014-4827(57)90013-7. [DOI] [PubMed] [Google Scholar]
  15. Pirson P., Steiger R. F., Trouet A., Gillet J., Herman F. Primaquine liposomes in the chemotherapy of experimental murine malaria. Ann Trop Med Parasitol. 1980 Aug;74(4):383–391. doi: 10.1080/00034983.1980.11687359. [DOI] [PubMed] [Google Scholar]
  16. Pirson P., Steiger R., Trouet A. The disposition of free and liposomally encapsulated antimalarial primaquine in mice. Biochem Pharmacol. 1982 Nov 1;31(21):3501–3507. doi: 10.1016/0006-2952(82)90633-5. [DOI] [PubMed] [Google Scholar]
  17. Smith J. E., Pirson P., Sinden R. E. Studies on the kinetics of uptake and distribution of free and liposome-entrapped primaquine, and of sporozoites by isolated perfused rat liver. Ann Trop Med Parasitol. 1983 Aug;77(4):379–386. doi: 10.1080/00034983.1983.11811725. [DOI] [PubMed] [Google Scholar]
  18. Souto-Padrón T., de Carvalho T. U., Chiari E., de Souza W. Further studies on the cell surface charge of Trypanosoma cruzi. Acta Trop. 1984 Sep;41(3):215–225. [PubMed] [Google Scholar]
  19. Szoka F., Jr, Papahadjopoulos D. Comparative properties and methods of preparation of lipid vesicles (liposomes). Annu Rev Biophys Bioeng. 1980;9:467–508. doi: 10.1146/annurev.bb.09.060180.002343. [DOI] [PubMed] [Google Scholar]
  20. Trouet A. U., Pirson P., Steiger R., Masquelier M., Baurain R., Gillet J. Development of new derivatives of primaquine by association with lysosomotropic carriers. Bull World Health Organ. 1981;59(3):449–458. [PMC free article] [PubMed] [Google Scholar]
  21. Turner M. J. Biochemistry of the variant surface glycoproteins of salivarian trypanosomes. Adv Parasitol. 1982;21:69–153. doi: 10.1016/s0065-308x(08)60275-4. [DOI] [PubMed] [Google Scholar]
  22. Waggoner A. S., Stryer L. Fluorescent probes of biological membranes. Proc Natl Acad Sci U S A. 1970 Oct;67(2):579–589. doi: 10.1073/pnas.67.2.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Weldon J. S., Munnell J. F., Hanson W. L., Alving C. R. Liposomal chemotherapy in visceral leishmaniasis: an ultrastructural study of an intracellular pathway. Z Parasitenkd. 1983;69(4):415–424. doi: 10.1007/BF00927697. [DOI] [PubMed] [Google Scholar]
  24. Yoshihara E., Nakae T. Cytolytic activity of liposomes containing stearylamine. Biochim Biophys Acta. 1986 Jan 16;854(1):93–101. doi: 10.1016/0005-2736(86)90068-4. [DOI] [PubMed] [Google Scholar]
  25. Yoshihara E., Tachibana H., Nakae T. Trypanocidal activity of the stearylamine-bearing liposome in vitro. Life Sci. 1987 Jun 1;40(22):2153–2159. doi: 10.1016/0024-3205(87)90005-1. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES