title: Enhanced paromomycin efficacy by solid lipid nanoparticle formulation against Leishmania in mice model.
abstract: Leishmaniasis caused by protozoan parasites of the genus Leishmania. Intracellular infections treatment such as leishmaniasis is frequently hampered by limited access of drugs to infected cells. Moreover, most of the current drugs are confined to some toxic compounds, and there are increasing incidences of development of drug resistance. Hence, production of a new antileishmanial compound is crucial. Paromomycin sulphate (PM) is a promising antileishmanial drug. One strategy to improve drug effectiveness is to use appropriate delivery systems. Solid lipid nanoparticle (SLN) is as an excellent substitute delivery system to other colloidal carrier. In the present study, PM was loaded in solid lipid nanoparticles (PM-SLN) and the in vivo efficacy was studied against Leishmania (L.) major-infected BALB/c mice. For this reason, the footpad swelling was measured and real-time PCR was performed to quantify the parasite load after infectious challenge. The level of cytokines including interleukin-4 (IL-4) and gamma interferon (IFN-γ) and nitric oxide was evaluated. Altogether, this study showed that the PM-SLN formulation is a safe compound and SLN in PM-SLN compound is effective for treatment of leishmaniasis by improving the effectiveness of PM in killing the parasite and switching towards Th1 response.
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Heidari-Kharaji
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: T
authors.initials: T
authors.lastname: Taheri
authors.affiliation: Regulatory Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: D
authors.initials: D
authors.lastname: Doroud
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Habibzadeh
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Badirzadeh
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran. s_rafati@yahoo.com, sima-rafatisy@pasteur.ac.ir.
authors.forename: S
authors.initials: S
authors.lastname: Rafati
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy* / Q000469:parasitology; D008055:Lipids; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009569:Nitric Oxide / Q000378:metabolism; D010303:Paromomycin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D016207:Cytokines; D004337:Drug Carriers; D008055:Lipids; D015847:Interleukin-4; D009569:Nitric Oxide; D010303:Paromomycin; D007371:Interferon-gamma
keywords: cutaneous leishmaniasis; cytokine; drug delivery system; paromomycin sulphate; solid lipid nanoparticle; therapy