Targeted delivery of paromomycin in murine infectious diseases through association to nano lipid systems

• Published in: Nanomedicine Vol. 11; no. 7; pp. 1851 - 1860
• Main Authors: Gaspar, Maria Manuela, PhD, Calado, Susana, Pereira, Joana, Ferronha, Helena, PhD, Correia, Ivone, Castro, Helena, PhD, Tomás, Ana M., PhD, Cruz, Maria Eugénia Meirinhos, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2015
• Subjects: Animals; Communicable Diseases - drug therapy; Communicable Diseases - microbiology; Communicable Diseases - parasitology; Disease Models, Animal; Drug Carriers; Drug Delivery Systems; Humans; Internal Medicine; Intracellular infections; Leishmania - drug effects; Leishmania - pathogenicity; Lipids - administration & dosage; Lipids - chemistry; Liposomes; Liposomes - administration & dosage; Liposomes - chemistry; Mice; Murine models; Mycobacterium - drug effects; Mycobacterium - pathogenicity; Paromomycin; Paromomycin - administration & dosage; Paromomycin - chemistry; Tissue Distribution; Liposomes; Murine models; Paromomycin; Intracellular infections
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2015.06.008

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. From the Clinical Editor 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.