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Article
A Targeted and Adjuvanted Nanocarrier Lowers the Effective Dose of Liposomal Amphotericin B and Enhances Adaptive Immunity in Murine Cutaneous Leishmaniasis
International Journal of Infectious Diseases
  • Pirouz M. Daftarian, University of Miami
  • Geoffrey W. Stone, University of Miami
  • Leticia Kovalski, University of Miami
  • Manoj Kumar, University of Miami
  • Aram Vosoughi, University of Miami
  • Maitee Urbieta, University of Miami
  • Patricia Blackwelder, University of Miami
  • Emre Dikici, University of Miami
  • Stephanie Duffort, University of Miami
  • Richard Boodoo, University of Miami
  • Alheli Rodriguez-Cortes, Universität Autonoma de Barcelona - Italy
  • Vance Lemmon, University of Miami
  • Sapna Deo, University of Miami
  • Jordi Alberola, Universität Autonoma de Barcelona - Italy
  • Victor L. Perez, University of Miami
  • Sylvia Daunert, University of Miami
  • Arba L. Ager, University of Miami
Document Type
Article
Publication Date
12-1-2013
Keywords
  • Immunochemotherapy,
  • Nanocarrier,
  • Adoptive immunity,
  • Intracellular,
  • Obligate intracellular parasites,
  • Leishmaniasis,
  • Vaccine
Peer Reviewed
1
Abstract
Background: Amphotericin B (AmB), the most effective drug against leishmaniasis, has serious toxicity. As Leishmania species are obligate intracellular parasites of antigen presenting cells (APC), an immunopotentiating APC-specific AmB nanocarrier would be ideally suited to reduce the drug dosage and regimen requirements in leishmaniasis treatment. Here, we report a nanocarrier that results in effective treatment shortening of cutaneous leishmaniasis in a mouse model, while also enhancing L. major specific T-cell immune responses in the infected host. Methods: We used a Pan-DR-binding epitope (PADRE)-derivatized-dendrimer (PDD), complexed with liposomal amphotericin B (LAmB) in an L. major mouse model and analyzed the therapeutic efficacy of low-dose PDD/ LAmB vs full dose LAmB. Results: PDD was shown to escort LAmB to APCs in vivo, enhanced the drug efficacy by 83% and drug APC targeting by 10-fold and significantly reduced parasite burden and toxicity. Fortuitously, the PDD immunopotentiating effect significantly enhanced parasite-specific T-cell responses in immunocompetent infected mice. Conclusions: PDD reduced the effective dose and toxicity of LAmB and resulted in elicitation of strong parasite specific T-cell responses. A reduced effective therapeutic dose was achieved by selective LAmB delivery to APC, bypassing bystander cells, reducing toxicity and inducing antiparasite immunity.
Comments

©The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Additional Comments
DOD grant #: DAMD 17-03-20021; National Institutes of Health grant #: P30AI073961
DOI
10.1093/infdis/jit378
Citation Information
Pirouz M. Daftarian, Geoffrey W. Stone, Leticia Kovalski, Manoj Kumar, et al.. "A Targeted and Adjuvanted Nanocarrier Lowers the Effective Dose of Liposomal Amphotericin B and Enhances Adaptive Immunity in Murine Cutaneous Leishmaniasis" International Journal of Infectious Diseases Vol. 208 Iss. 11 (2013) p. 1914 - 1922 ISSN: 1201-9712
Available at: http://works.bepress.com/patricia-blackwelder/1/