title: Photodynamic ultradeformable liposomes: Design and characterization.
abstract: Hydrophobic ([tetrakis(2,4-dimetil-3-pentyloxi)-phthalocyaninate]zinc(II)) (ZnPc) and hydrophilic ([tetrakis(N,N,N-trimethylammoniumetoxi)-phthalocyaninate]zinc(II) tetraiodide) (ZnPcMet) phthalocyanines were synthesized and loaded in ultradeformable liposomes (UDL) of soybean phosphatidylcholine and sodium cholate (6:1, w/w, ratio), resulting 100 nm mean size vesicles of negative Zeta potential, with encapsulation efficiencies of 85 and 53%, enthalpy of phase transition of 5.33 and 158 J/mmol for ZnPc and ZnPcMet, respectively, indicating their deep and moderate partition into UD matrices. Matrix elasticity of UDL-phthalocyanines resulted 28-fold greater than that of non-UDL, leaking only 25% of its inner aqueous content after passage through a nanoporous barrier versus 100% leakage for non-UDL. UDL-ZnPc made ZnPc soluble in aqueous buffer while kept the monomeric state, rendering singlet oxygen quantum yield (Phi(Delta)) similar to that obtained in ethanol (0.61), whereas UDL-ZnPcMet had a four-fold higher Phi(Delta) than that of free ZnPcMet (0.21). Free phthalocyanines were non-toxic at 1 and 10 microM, both in dark or upon irradiation at 15 J/cm2 on Vero and J-774 cells (MTT assay). Only liposomal ZnPc at 10 microM was toxic for J-774 cells under both conditions. Additionally, endo-lysosomal confinement of the HPTS dye was kept after irradiation at 15 J/cm2 in the presence of UDL-phtalocyanines. This could lead to improve effects of singlet oxygen against intra-vesicular pathogen targets inside the endo-lysosomal system.
authors.affiliation: Laboratorio de Diseño de Estrategias de Targeting de Drogas (LDTD), Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Peña 180, Bernal B1876BXD, Buenos Aires, Argentina.
authors.forename: J
authors.initials: J
authors.lastname: Montanari
authors.forename: A P
authors.initials: AP
authors.lastname: Perez
authors.forename: F
authors.initials: F
authors.lastname: Di Salvo
authors.forename: V
authors.initials: V
authors.lastname: Diz
authors.forename: R
authors.initials: R
authors.lastname: Barnadas
authors.forename: L
authors.initials: L
authors.lastname: Dicelio
authors.forename: F
authors.initials: F
authors.lastname: Doctorovich
authors.forename: M J
authors.initials: MJ
authors.lastname: Morilla
authors.forename: E L
authors.initials: EL
authors.lastname: Romero
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D007211:Indoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D054833:Isoindoles; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy; D008081:Liposomes / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology; D010778:Photochemotherapy / Q000379:methods; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D014709:Vero Cells
chemical_list: D007211:Indoles; D054833:Isoindoles; D008081:Liposomes; D011838:Radiation-Sensitizing Agents; C013647:phthalocyanine