PURPOSE: 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.
PURPOSE: 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: Xavier García-Del-Muro; Antonio López-Pousa; Joan Maurel; Javier Martín; Javier Martínez-Trufero; Antonio Casado; Auxiliadora Gómez-España; Joaquín Fra; Josefina Cruz; Andrés Poveda; Andrés Meana; Carlos Pericay; Ricardo Cubedo; Jordi Rubió; Ana De Juan; Nuria Laínez; Juan Antonio Carrasco; Raquel de Andrés; José M Buesa Journal: J Clin Oncol Date: 2011-05-23 Impact factor: 44.544
Authors: R Moog; A M Burger; M Brandl; J Schüler; R Schubert; C Unger; H H Fiebig; U Massing Journal: Cancer Chemother Pharmacol Date: 2002-03-12 Impact factor: 3.333
Authors: Lars H Lindner; Martin E Eichhorn; Hansjoerg Eibl; Nicole Teichert; Marcus Schmitt-Sody; Rolf D Issels; Marc Dellian Journal: Clin Cancer Res Date: 2004-03-15 Impact factor: 12.531
Authors: J L Abbruzzese; R Grunewald; E A Weeks; D Gravel; T Adams; B Nowak; S Mineishi; P Tarassoff; W Satterlee; M N Raber Journal: J Clin Oncol Date: 1991-03 Impact factor: 44.544
Authors: Mariella Tutter; Christina Schug; Kathrin A Schmohl; Sarah Urnauer; Carolin Kitzberger; Nathalie Schwenk; Matteo Petrini; Christian Zach; Sibylle Ziegler; Peter Bartenstein; Wolfgang A Weber; Gabriele Multhoff; Ernst Wagner; Lars H Lindner; Peter J Nelson; Christine Spitzweg Journal: Mol Ther Date: 2020-10-15 Impact factor: 11.454
Authors: Matteo Petrini; Wouter J M Lokerse; Agnieszka Mach; Martin Hossann; Olivia M Merkel; Lars H Lindner Journal: Int J Nanomedicine Date: 2021-06-14
Authors: Helena C Besse; Clemens Bos; Maurice M J M Zandvliet; Kim van der Wurff-Jacobs; Chrit T W Moonen; Roel Deckers Journal: PLoS One Date: 2018-09-18 Impact factor: 3.240