Liposomal resiquimod for the treatment of Leishmania donovani infection

• Published in: Journal of antimicrobial chemotherapy Vol. 69; no. 1; pp. 168 - 175
• Main Authors: Peine, Kevin J, Gupta, Gaurav, Brackman, Deanna J, Papenfuss, Tracey L, Ainslie, Kristy M, Satoskar, Abhay R, Bachelder, Eric M
• Format: Journal Article
• Language: English
• Published: England Oxford Publishing Limited (England) 01.01.2014; Oxford University Press
• Subjects: Administration, Intravenous; Animals; Antiprotozoal Agents - administration & dosage; Antiviral drugs; Bone Marrow - parasitology; Disease Models, Animal; Drug therapy; Experiments; Imidazoles - administration & dosage; Interferon-gamma - secretion; Interleukin-10 - secretion; Leishmania donovani; Leishmania donovani - drug effects; Leishmania donovani - isolation & purification; Leishmaniasis, Visceral - drug therapy; Leishmaniasis, Visceral - parasitology; Leukocytes, Mononuclear - immunology; Liposomes - administration & dosage; Liver - parasitology; Mice; Mice, Inbred BALB C; Original Research; Parasite Load; Parasitic protozoa; Prescription drugs; Spleen - parasitology; Treatment Outcome; visceral; drug delivery; therapy; imidazoquinoline
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkt320

The imidazoquinoline family of drugs are Toll-like receptor 7/8 agonists that have previously been used in the treatment of cutaneous leishmaniasis. Because of the hydrophobic nature of imidazoquinolines, they are traditionally not administered systemically for the treatment of visceral leishmaniasis. We formulated liposomal resiquimod, an imidazoquinoline, for the systemic treatment of visceral leishmaniasis. By using lipid film hydration with extrusion, we encapsulated resiquimod in liposomes. These liposomes were then injected intravenously to treat BALB/c mice infected with Leishmania donovani. Treatment with liposomal resiquimod significantly decreased the parasite load in the liver, spleen and bone marrow. In addition, resiquimod treatment increased interferon-γ and interleukin-10 production in an antigen recall assay. Resiquimod was shown to be non-toxic in histology and in vitro culture experiments. FDA-approved resiquimod, in a liposomal formulation, displays promising results in treating visceral leishmaniasis.