Authors: E.V. Tazina, A.V. Polozkova, O.L. Orlova, E.V. Ignatieva, V.V. Mescherikova, A. Wainson, S.P. Yarmonenko, N.A. Oborotova
Affilation: N.N. Blokhin Russian Cancer Research Center of RAMS, Russian Federation
Pages: 53 - 56
Keywords: doxorubicin, thermosensitive liposomes, hyperthermia, melanoma B-16, Ehrlich carcinoma
Purpose: Preparation of thermoliposomes with doxorubicin and investigation of their effect on solid Ehrlich carcinoma and B-16 mouse melanoma in combination with hyperthermia. Materials and methods: Thermosensitive liposomes were prepared using DPPC, DSPC, DSPE-PEG 2000 and cholesterol (9:1:0.02:0.2 m/m). Doxorubicin (Dox) was loaded into thermoliposomes by ammonium ion gradient. For better stabilization thermoliposomes with doxorubicin were lyophilized. Tumors were transplanted in the shank muscle of mice. Thermoliposomes loaded with Dox or free Dox were administered in retroorbital sinus at different doses. In experiments in vitro thermoliposomes or free Dox were added to melanoma B-16 cell suspension. Hyperthermia was performed at 42.5-43 °C for 30-60 min. Results: Mean diameter of lyophilized thermoliposomes was 170 ± 10 nm. Thermosensitive liposomes encapsulated 73-94 % of doxorubicin. In experiments in vitro done with thermoliposomes the cell death increased 5-fold when cell suspension was incubated at elevated temperature instead of 37 °C. The doubling time of tumors was 9 days after heating on a background of Dox administration at dose of 9 mg/kg, while heating of tumors after administration of thermoliposomes loaded with Dox at doses of 4.5 and 9 mg/kg increased tumor doubling time up to 12 and 18 days respectively.