RESUMEN
Preclinical study of therapeutic properties of an innovative drug Doxorubicin-NPh (doxorubicin in the form of ultrafine suspension of phospholipid liposomes) in comparison with free doxorubicin (Doxorubicin-Teva) and protected doxorubicin (Caelyx) was performed on transplanted murine tumor models. All these drugs were efficient in Ca755 breast carcinoma model (tumor growth inhibition ≈100%, increase in lifespan 90.6-114.3%). In P388 lymphocytic leukemia and LLC lung carcinoma, advantages of the protected doxorubicin by the benefit/risk ratio (width of therapeutic interval) were demonstrated: Caelyx>Doxorubicin-NPh>Doxorubicin-Teva. Doxorubicin-NPh and Caelyx exhibited similar therapeutic activity in the LLC model, especially when administered 3 times with 3-day intervals; for Doxorubicin-Teva, the optimal interval between the injections was 7 days.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacología , Leucemia P388/tratamiento farmacológico , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Aloinjertos , Animales , Antibióticos Antineoplásicos/farmacocinética , Carcinoma Pulmonar de Lewis/patología , Doxorrubicina/farmacocinética , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Leucemia P388/patología , Liposomas/química , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Fosfolípidos/química , Polietilenglicoles/farmacocinética , Polietilenglicoles/farmacología , Carga Tumoral/efectos de los fármacosRESUMEN
Antitumor efficacy of the combined suicide gene therapy and radiotherapy was studied on the model of CT26 murine colon adenocarcinoma. CMV-FCU1-IRES-mGM-CSF-pGL3 construct with PEG-PEI-TAT (FCU1-mGM/5-FC) block copolymer as a vector was used for intratumoral administration. Tumors were irradiated with a single 5 Gy dose. The efficacy was evaluated according to the grade of tumor growth inhibition (T/C) and lifespan of the animals. Pronounced antitumor activity of the combined use of FCU1-mGM/5-FC system with radiotherapy on the background of prolonged lifespan and the synergism of the applied methods was revealed.