A targeted and adjuvanted nanocarrier lowers the effective dose of liposomal amphotericin B and enhances adaptive immunity in murine cutaneous leishmaniasis.

Published

Journal Article

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.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.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.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.

Full Text

Duke Authors

Cited Authors

  • Daftarian, PM; Stone, GW; Kovalski, L; Kumar, M; Vosoughi, A; Urbieta, M; Blackwelder, P; Dikici, E; Serafini, P; Duffort, S; Boodoo, R; Rodríguez-Cortés, A; Lemmon, V; Deo, S; Alberola, J; Perez, VL; Daunert, S; Ager, AL

Published Date

  • December 2013

Published In

Volume / Issue

  • 208 / 11

Start / End Page

  • 1914 - 1922

PubMed ID

  • 23901083

Pubmed Central ID

  • 23901083

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

International Standard Serial Number (ISSN)

  • 0022-1899

Digital Object Identifier (DOI)

  • 10.1093/infdis/jit378

Language

  • eng