title: Drug Targeting to Macrophages With Solid Lipid Nanoparticles Harboring Paromomycin: an In Vitro Evaluation Against L. major and L. tropica.
abstract: Leishmaniasis is a worldwide disease that leads to high mortality and morbidity in human populations. Today, leishmaniasis is managed via drug therapy. The drugs that are already in clinical use are limited to a number of toxic chemical compounds and their parasite drug resistance is increasing. It is therefore essential, in order to circumvent the current difficulties, to design a new anti-leishmanial drug treatment strategy. Besides producing new, active anti-leishmanial entities, another promising strategy could be developing novel delivery systems and formulations of the existing pharmaceutical ingredients to improve drug efficacy. In the present study, paromomycin sulfate (PM), as one of the promising anti-leishmanial drugs, was formulated in solid lipid nanoparticles (SLN), and its in vitro efficacy was investigated against different strains of Leishmania using a MTT test, Parasite-Rescue-Transformation-Assay, SYTO Green staining, and fluorescent microscope imaging. The results show that PM-loaded SLN is significantly more effective than PM in inhibiting parasite propagation (P < 0.05) and that cytotoxicity of PM-SLN formulations is size dependent. According to our results, delivery of the drugs to the macrophages via nanoparticle utilization seems to be an accessible and practical approach.
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Maryam Heidari
authors.initials: MH
authors.lastname: Kharaji
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: Tahereh
authors.initials: T
authors.lastname: Taheri
authors.affiliation: Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran. s_rafati@yahoo.com.
authors.forename: Sima
authors.initials: S
authors.lastname: Rafati
mesh_terms: D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D008055:Lipids / Q000008:administration & dosage*; D008264:Macrophages / Q000187:drug effects*; D053758:Nanoparticles / Q000008:administration & dosage*; D010303:Paromomycin / Q000008:administration & dosage*
chemical_list: D008055:Lipids; D010303:Paromomycin
keywords: cutaneous leishmaniasis; drug delivery system; paromomycin sulfate; solid lipid nanoparticle