title: Gemcitabine treatment of rat soft tissue sarcoma with phosphatidyldiglycerol-based thermosensitive liposomes.
abstract: OBJECTIVE
  The pyrimidine analogue gemcitabine (dFdC) is frequently used in the treatment of patients with solid tumors. However, after i.v. application dFdC is rapidly inactivated by metabolization. Here, the potential of thermosensitive liposomes based on 1,2-dipalmitoyl-sn-glycero-3-phosphodiglycerol (DPPG2-TSL) were investigated as carrier and targeting system for delivery of dFdC in combination with local hyperthermia (HT).
  
  
  METHODS
  DPPG2-TSL were prepared by the lipid film hydration and extrusion method and characterized by dynamic light scattering, thin layer chromatography, phosphate assay and HPLC. In vivo experiments were performed in Brown Norway rats with a syngeneic soft tissue sarcoma. Local HT treatment was performed by light exposure.
  
  
  RESULTS
  DPPG2-TSL were stable at 37°C in serum and showed a temperature dependent dFdC release >40°C. Plasma half-life of dFdC was strongly increased from 0.07 h (non-liposomal) to 0.53 h (liposomal, vesicle size 105 nm) or 2.59 h (liposomal, 129 nm). Therapy of BN175 tumors with dFdC encapsulated in DPPG2-TSL + HT showed significant improvement in tumor growth delay compared to non-liposomal dFdC without HT (p < 0.05), non-liposomal dFdC with HT (p < 0.01), and liposomal dFdC without HT (p < 0.05), respectively.
  
  
  CONCLUSIONS
  Gemcitabine encapsulated in DPPG2-TSL in combination with local HT is a promising tool for the treatment of solid tumors. Therefore, these encouraging results ask for further investigation and evaluation.
authors.affiliation: Department of Internal Medicine III, University Hospital Munich Ludwig-Maximilians University, Munich, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Limmer
authors.forename: Jasmin
authors.initials: J
authors.lastname: Hahn
authors.forename: Rebecca
authors.initials: R
authors.lastname: Schmidt
authors.forename: Kirsten
authors.initials: K
authors.lastname: Wachholz
authors.forename: Anja
authors.initials: A
authors.lastname: Zengerle
authors.forename: Katharina
authors.initials: K
authors.lastname: Lechner
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Eibl
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Issels
authors.forename: Martin
authors.initials: M
authors.lastname: Hossann
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lindner
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004317:Doxorubicin; D006207:Half-Life; D006979:Hyperthermia, Induced; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D010715:Phosphatidylglycerols / Q000737:chemistry; D051381:Rats; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D008081:Liposomes; D010715:Phosphatidylglycerols; D003841:Deoxycytidine; D004317:Doxorubicin; C030345:1,2-dipalmitoylphosphatidylglycerol; D000093542:Gemcitabine