title: Solid lipid nanoparticle loaded with paromomycin: in vivo efficacy against Leishmania tropica infection in BALB/c mice model.
abstract: Leishmaniasis is a parasitic disease transmitted through the bite of an infected phlebotomine sand fly and caused by protozoan parasites of the genus Leishmania. There is no available vaccine for leishmaniasis in human, and the current chemotherapy approaches are hampered by different clinical problems. Most of available drugs are confined to a limited number of toxic chemical compounds, which some parasite strains have evolved drug resistance against. Hence, drug discovery and production of a new anti leishmanial compound is essential. One promising strategy is using the nanoparticle delivery systems with the aim of accelerating the efficacy of the available treatments. In the present study, paromomycin sulfate (PM) was formulated in solid lipid nanoparticles (SLN) and the in vivo efficacy was investigated against Leishmania tropica in BALB/c mice model. To do so, the increase in footpad thickness was measured and real-time PCR was performed to quantify the parasite load after infectious challenge. The level of nitric oxide and cytokines including interleukin-4 (IL-4) and gamma interferon (IFN -γ) were assessed. Altogether, the results show that PM loaded into SLN is significantly more effective than PM alone in inhibiting the parasite propagation and switching towards Th1 response.
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Heidari-Kharaji
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Tahereh
authors.initials: T
authors.lastname: Taheri
authors.affiliation: Regulatory Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Delaram
authors.initials: D
authors.lastname: Doroud
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Sima
authors.initials: S
authors.lastname: Habibzadeh
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran. sima-rafatisy@pasteur.ac.ir.
authors.forename: Sima
authors.initials: S
authors.lastname: Rafati
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000627:therapeutic use*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007895:Leishmania tropica / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D010303:Paromomycin / Q000627:therapeutic use*; D018417:Th1 Cells / Q000276:immunology
chemical_list: D000981:Antiprotozoal Agents; D004337:Drug Carriers; D015847:Interleukin-4; D009569:Nitric Oxide; D010303:Paromomycin; D007371:Interferon-gamma
keywords: Cutaneous leishmaniasis; Drug delivery system; Paramomycin sulfate; Solid lipid nanoparticle; Therapy