title: Targeted delivery of paromomycin in murine infectious diseases through association to nano lipid systems.
abstract: Treatment of intracellular infections such as those caused by Mycobacterium spp. and Leishmania spp. is often hampered by limited access of drugs to infected cells. This is the case of paromomycin (PRM), an antibiotic with broad spectrum in vitro activity against protozoa and mycobacteria. Association of chemotherapeutics to liposomes is a worthy strategy to circumvent poor drug accessibility. Six different PRM liposomal formulations were produced, physicochemically characterized and biologically evaluated in a macrophagic cell line confirming their adequacy for in vivo studies. Biodistribution profiles of PRM liposomes revealed preferential targeting of the antibiotic to the liver, spleen and lungs, relative to free PRM, which translated into an enhanced therapeutic effect in murine models infected with Mycobacterium avium and Leishmania infantum and an absence of toxic effects. Our findings demonstrate the advantages of associating PRM to liposomes indicating their potential as an alternative therapeutic strategy for mycobacterial and parasite infections.
  
  
  BACKGROUND
  Infections caused by intracellular organisms such as Mycobacterium and Leishmania remain a significant problem worldwide. Although effective drugs are available, their actions are limited by access into the intracellular compartment. In this article, the authors developed different liposomal formulations as drug carriers of paromomycin and investigated their efficacy in a mouse model. The positive should provide another treatment option for these organisms in the near future.
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal. Electronic address: mgaspar@ff.ul.pt.
authors.forename: Maria Manuela
authors.initials: MM
authors.lastname: Gaspar
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Calado
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Pereira
authors.affiliation: Unidade de Investigação de Patologia e Microbiologia Animal, Instituto Nacional de Investigação Agrária e Veterinária, Lisboa, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Ferronha
authors.affiliation: Unidade de Investigação de Patologia e Microbiologia Animal, Instituto Nacional de Investigação Agrária e Veterinária, Lisboa, Portugal.
authors.forename: Ivone
authors.initials: I
authors.lastname: Correia
authors.affiliation: IBMC, Instituto de Biologia Molecular Celular, Porto, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Castro
authors.affiliation: IBMC, Instituto de Biologia Molecular Celular, Porto, Portugal; ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Tomás
authors.affiliation: Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Maria Eugénia Meirinhos
authors.initials: ME
authors.lastname: Cruz
mesh_terms: D000818:Animals; D003141:Communicable Diseases / Q000188:drug therapy* / Q000382:microbiology / Q000469:parasitology; D004195:Disease Models, Animal; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D007891:Leishmania / Q000187:drug effects / Q000472:pathogenicity; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D009161:Mycobacterium / Q000187:drug effects / Q000472:pathogenicity; D010303:Paromomycin / Q000008:administration & dosage* / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D010303:Paromomycin
keywords: Intracellular infections; Liposomes; Murine models; Paromomycin