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. 1987 Dec;31(12):1901–1903. doi: 10.1128/aac.31.12.1901

Toxicity and therapeutic effects in mice of liposome-encapsulated nystatin for systemic fungal infections.

R T Mehta 1, R L Hopfer 1, T McQueen 1, R L Juliano 1, G Lopez-Berestein 1
PMCID: PMC175824  PMID: 3439799

Abstract

The therapeutic activity of nystatin (NYS) incorporated in multilamellar liposomes (L-NYS) was studied in vivo. Hale-Stoner mice injected intravenously with various doses of L-NYS and free NYS showed a significant reduction in toxicity of NYS after the NYS was incorporated into liposomes (maximal tolerated doses, 16 and 4 mg/kg of body weight, respectively). The maximal tolerated dose of free NYS had no effect in the treatment of mice infected with Candida albicans, whereas L-NYS at an equivalent dose improved the survival of mice. A marked increase in survival was observed when L-NYS was administered in higher and multiple doses (total doses up to 80 mg/kg). Liposome encapsulation thus provided a means for intravenous administration of NYS, reducing its toxicity and making it an active systemic antifungal agent.

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Selected References

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  1. Carpentieri U., Haggard M. E., Lockhart L. H., Gustavson L. P., Box Q. T., West E. F. Clinical experience in prevention of candidiasis by nystatin in children with acute lymphocytic leukemia. J Pediatr. 1978 Apr;92(4):593–595. doi: 10.1016/s0022-3476(78)80298-4. [DOI] [PubMed] [Google Scholar]
  2. Edwards J. E., Jr, Lehrer R. I., Stiehm E. R., Fischer T. J., Young L. S. Severe candidal infections: clinical perspective, immune defense mechanisms, and current concepts of therapy. Ann Intern Med. 1978 Jul;89(1):91–106. doi: 10.7326/0003-4819-89-1-91. [DOI] [PubMed] [Google Scholar]
  3. GEHAN E. A. A GENERALIZED WILCOXON TEST FOR COMPARING ARBITRARILY SINGLY-CENSORED SAMPLES. Biometrika. 1965 Jun;52:203–223. [PubMed] [Google Scholar]
  4. Hamilton-Miller J. M. Chemistry and biology of the polyene macrolide antibiotics. Bacteriol Rev. 1973 Jun;37(2):166–196. [PMC free article] [PubMed] [Google Scholar]
  5. Jones P. G., Kauffman C. A., McAuliffe L. S., Liepman M. K., Bergman A. G. Efficacy of ketoconazole v nystatin in prevention of fungal infections in neutropenic patients. Arch Intern Med. 1984 Mar;144(3):549–551. [PubMed] [Google Scholar]
  6. Lopez-Berestein G., Fainstein V., Hopfer R., Mehta K., Sullivan M. P., Keating M., Rosenblum M. G., Mehta R., Luna M., Hersh E. M. Liposomal amphotericin B for the treatment of systemic fungal infections in patients with cancer: a preliminary study. J Infect Dis. 1985 Apr;151(4):704–710. doi: 10.1093/infdis/151.4.704. [DOI] [PubMed] [Google Scholar]
  7. Lopez-Berestein G., Hopfer R. L., Mehta R., Mehta K., Hersh E. M., Juliano R. L. Liposome-encapsulated amphotericin B for treatment of disseminated candidiasis in neutropenic mice. J Infect Dis. 1984 Aug;150(2):278–283. doi: 10.1093/infdis/150.2.278. [DOI] [PubMed] [Google Scholar]
  8. Lopez-Berestein G., Hopfer R. L., Mehta R., Mehta K., Hersh E. M., Juliano R. L. Liposome-encapsulated amphotericin B for treatment of disseminated candidiasis in neutropenic mice. J Infect Dis. 1984 Aug;150(2):278–283. doi: 10.1093/infdis/150.2.278. [DOI] [PubMed] [Google Scholar]
  9. Lopez-Berestein G., Rosenblum M. G., Mehta R. Altered tissue distribution of amphotericin B by liposomal encapsulation: comparison of normal mice to mice infected with Candida albicans. Cancer Drug Deliv. 1984 Summer;1(3):199–205. doi: 10.1089/cdd.1984.1.199. [DOI] [PubMed] [Google Scholar]
  10. Mehta R. T., Hopfer R. L., Gunner L. A., Juliano R. L., Lopez-Berestein G. Formulation, toxicity, and antifungal activity in vitro of liposome-encapsulated nystatin as therapeutic agent for systemic candidiasis. Antimicrob Agents Chemother. 1987 Dec;31(12):1897–1900. doi: 10.1128/aac.31.12.1897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Meunier-Carpentier F. Symposium on infectious complications of neoplastic disease (Part II). Chemoprophylaxis of fungal infections. Am J Med. 1984 Apr;76(4):652–656. doi: 10.1016/0002-9343(84)90290-0. [DOI] [PubMed] [Google Scholar]
  12. Rahman A., White G., More N., Schein P. S. Pharmacological, toxicological, and therapeutic evaluation in mice of doxorubicin entrapped in cardiolipin liposomes. Cancer Res. 1985 Feb;45(2):796–803. [PubMed] [Google Scholar]
  13. Richardson V. J. Liposomes in antimicrobial chemotherapy. J Antimicrob Chemother. 1983 Dec;12(6):532–534. doi: 10.1093/jac/12.6.532. [DOI] [PubMed] [Google Scholar]
  14. Young L. S. The outlook for antifungal prophylaxis in the compromised host. J Antimicrob Chemother. 1982 May;9(5):338–340. doi: 10.1093/jac/9.5.338. [DOI] [PubMed] [Google Scholar]

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