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

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

The Journal of infectious diseases (2013-08-01)
Pirouz M Daftarian, Geoffrey W Stone, Leticia Kovalski, Manoj Kumar, Aram Vosoughi, Maitee Urbieta, Pat Blackwelder, Emre Dikici, Paolo Serafini, Stephanie Duffort, Richard Boodoo, Alhelí Rodríguez-Cortés, Vance Lemmon, Sapna Deo, Jordi Alberola, Victor L Perez, Sylvia Daunert, Arba L Ager
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Amphotericin B from Streptomyces sp., ~80% (HPLC), powder
Sigma-Aldrich
Amphotericin B from Streptomyces sp., BioReagent, suitable for cell culture, ~80% (HPLC)
Supelco
Amphotericin B trihydrate, VETRANAL®, analytical standard
Sigma-Aldrich
Amphotericin B solution, 250 μg/mL in deionized water, 0.1 μm filtered, BioReagent, suitable for cell culture
Amphotericin B for peak identification, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Amphotericin B solubilized, powder, γ-irradiated, BioXtra, suitable for cell culture