title: In vitro phototoxicity of ultradeformable liposomes containing chloroaluminum phthalocyanine against New World Leishmania species.
abstract: The use of photodynamic therapy (PDT) against cutaneous leishmaniasis (CL) based on chloroaluminum phthalocyanine (ClAlPc) is a promissory alternative therapy. The main purpose of this article was to assess the internalization and in vitro phototoxic activities of ClAlPc encapsulated in ultradeformable liposomes (UDL-ClAlPc) in Leishmania parasites and mammalian cells. Cell internalization was determined by fluorescence microscopy, cell and parasite damage by standard MTT or direct microscopic analysis and a phototoxic index (PI) was calculated as the compound activity (IC(50)) at 0 J/cm(2)/IC(50) at 17 J/cm(2). Liposomal and free ClAlPc were internalized by infected and non-infected THP-1 cells and co-localized in the mitochondria. Treatment of UDL-ClAlPc was almost 10 times more photoactive than free ClAlPc on THP-1 cells and promastigotes and intracellular amastigotes of Leishmania chagasi and Leishmania panamensis. Liposomal compounds were active on non-irradiated and irradiated cells however PI higher than 50 were calculated. PI for amphotericin B referential drug were lower than 1.2. Empty liposomes tested at the same lipid concentration of active ClPcAl-liposomes were non-toxic. Upon photodynamic treatment a nonselective-parasite activity against intracellular amastigotes were observed and loss of membrane integrity resulting in a release of parasites was detected. Further studies oriented to evaluate both the state of infection after PDT and the effectiveness of UDL as delivery vehicles of ClAlPc in CL experimental models are required.
authors.affiliation: Centro de Investigación en Enfermedades Tropicales (CINTROP), Escuela de Medicina, Departamento de Ciencias Básicas, Universidad Industrial de Santander, Bucaramanga, Colombia. indiraher@gmail.com
authors.forename: Indira Paola
authors.initials: IP
authors.lastname: Hernández
authors.forename: Jorge
authors.initials: J
authors.lastname: Montanari
authors.forename: Wilfredo
authors.initials: W
authors.lastname: Valdivieso
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Morilla
authors.forename: Eder Lilia
authors.initials: EL
authors.lastname: Romero
authors.forename: Patricia
authors.initials: P
authors.lastname: Escobar
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D008081:Liposomes; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D013045:Species Specificity
chemical_list: D007211:Indoles; D008081:Liposomes; D009942:Organometallic Compounds; D010743:Phospholipids; D017319:Photosensitizing Agents; C044797:chloroaluminum phthalocyanine