抄録
We have reported that temperature-sensitive liposomes containing adriamycin (TS-Lip-ADM) mainly delivered ADM to heated tumors with local hyperthermia and enhanced antitumor effect. TS-Lip-ADM composed of DPPC (Tc= 41°C) (type-I) released considerable amount of ADM in the blood stream, making its clinical application difficult. To raise the stability of the liposomes, we included various ratio of DSPC (Tc = 54°C) and/or cholesterol (Chol) in the liposomal membrane and assessed temperature sensitivity. Addition of DSPC reduced ADM leakage from the liposomes at lower than 40°C and raised the maximal releasing temperature. Chol makes liposomes more stable in the presence of serum. TS-Lip-ADM including Chol up to 20 mol% remained temperature-sensitive. Inclusion of 30 mol% Chol abolished this characteristic. We made TS-Lip-ADM composed of DPPC, DSPC and Chol, in the molar ratio 7 : 1 : 2 (type-II), and investigated the selective delivery of ADM from type-II to NUE human hepatoma cells inoculated in nude mice and antitumor effect evaluated by the tumor weights, compared with type-I. NUE tumor uptake of ADM was increased by local hyperthermia at 42 °C for 30 min. ADM concentration in heated type-II tumors was about three times as high as in heated free ADM tumors, but not different from type-I significantly. Hyperthrarmia enhanced the antitumor effect.
