title: A new liposomal formulation of Gemcitabine is active in an orthotopic mouse model of pancreatic cancer accessible to bioluminescence imaging.
abstract: Despite its rapid enzymatic inactivation and therefore limited activity in vivo, Gemcitabine is the standard drug for pancreatic cancer treatment. To protect the drug, and achieve passive tumor targeting, we developed a liposomal formulation of Gemcitabine, GemLip (Ø: 36 nm: 47% entrapment). Its anti-tumoral activity was tested on MIA PaCa-2 cells growing orthotopically in nude mice. Bioluminescence measurement mediated by the stable integration of the luciferase gene was employed to randomize the mice, and monitor tumor growth. GemLip (4 and 8 mg/kg), Gemcitabine (240 mg/kg), and empty liposomes (equivalent to 8 mg/kg GemLip) were injected intravenously once weekly for 5 weeks. GemLip (8 mg/kg) stopped tumor growth, as measured via in vivo bioluminescence, reducing the primary tumor size by 68% (SD +/- 8%; p < 0.02), whereas Gemcitabine hardly affected tumor size (-7%; +/- 1.5%). In 80% of animals, luciferase activity in the liver indicated the presence of metastases. All treatments, including the empty liposomes, reduced the metastatic burden. Thus, GemLip shows promising antitumoral activity in this model. Surprisingly, empty liposomes attenuate the spread of metastases similar to Gemcitabine and GemLip. Further, luciferase marked tumor cells are a powerful tool to observe tumor growth in vivo, and to detect and quantify metastases.
authors.affiliation: Department of General and Visceral Surgery, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Bornmann
authors.forename: R
authors.initials: R
authors.lastname: Graeser
authors.forename: N
authors.initials: N
authors.lastname: Esser
authors.forename: V
authors.initials: V
authors.lastname: Ziroli
authors.forename: P
authors.initials: P
authors.lastname: Jantscheff
authors.forename: T
authors.initials: T
authors.lastname: Keck
authors.forename: C
authors.initials: C
authors.lastname: Unger
authors.forename: U T
authors.initials: UT
authors.lastname: Hopt
authors.forename: U
authors.initials: U
authors.lastname: Adam
authors.forename: C
authors.initials: C
authors.lastname: Schaechtele
authors.forename: U
authors.initials: U
authors.lastname: Massing
authors.forename: E
authors.initials: E
authors.lastname: von Dobschuetz
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D002199:Capillary Permeability / Q000187:drug effects; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers; D004339:Drug Compounding; D005070:Evans Blue; D008081:Liposomes; D008156:Luciferases / Q000235:genetics; D049449:Luminescence; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D010539:Permeability; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D003841:Deoxycytidine; D005070:Evans Blue; D008156:Luciferases; D000093542:Gemcitabine