title: Preparation, characterization and in vitro evaluation of sterically stabilized liposome containing a naphthalenediimide derivative as anticancer agent.
abstract: The aim of this study was to incorporate a new naphthalenediimide derivative (AN169) with a promising anticancer activity into pegylated liposomes to an extent that allows its in vitro and in vivo testing without use of toxic solvent. AN169-loaded liposomes were prepared using the thin-film hydration method and characterized for size, polydispersity index, drug content and drug release. We examined their lyophilization ability in the presence of cryoprotectants (trehalose, sucrose and lysine) and the long-term stability of the lyophilized products stored at 4 °C for 3 and 6 months by particle size changes and drug leakage. AN169 was successfully loaded into liposomes with an entrapment efficiency of 87.3 ± 2.5%. The hydrodynamic diameter of these liposomes after sonication was ∼ 145 nm with a high degree of monodispersity. Trehalose was found to be superior to the other lyoprotectants. In particular, trehalose 1:10 lipid:cryoprotectant molar ratio may provide stable lyophilized liposomes with the conservation of physicochemical properties upon freeze-drying and long-term storage conditions. We also assessed their in vitro antitumor activity in human cancer cell lines (HTLA-230 neuroblastoma, Mel 3.0 melanoma, OVCAR-3 ovarian carcinoma and SV620 prostate cancer cells). However, only after 72 h incubation, loaded liposomes showed almost the same IC50 as free AN169. In conclusion, we developed a stable lyophilized liposomal formulation for intravenous administration of AN169 as anticancer drug, with the advantage of avoiding the use of potentially toxic solubilizing agents for future in vivo experiments.
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum University of Bologna , Rimini , Italy and.
authors.forename: Amelia
authors.initials: A
authors.lastname: Parise
authors.forename: Andrea
authors.initials: A
authors.lastname: Milelli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tumiatti
authors.forename: Anna
authors.initials: A
authors.lastname: Minarini
authors.forename: Paolo
authors.initials: P
authors.lastname: Neviani
authors.forename: Guendalina
authors.initials: G
authors.lastname: Zuccari
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001596:Benzylamines / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004354:Drug Screening Assays, Antitumor; D005612:Freeze Drying; D006801:Humans; D007094:Imides; D066298:In Vitro Techniques; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology*; D009281:Naphthalenes; D053644:Naphthalimides / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology
chemical_list: C000606996:AN169 compound; D000970:Antineoplastic Agents; D001596:Benzylamines; D007094:Imides; D008081:Liposomes; D009281:Naphthalenes; D053644:Naphthalimides; C542131:naphthalenediimide; D011092:Polyethylene Glycols
keywords: Cancer therapy; DNA-intercalating ligands; drug delivery system; intravenous administration; naphthalenediimide