IMPROVEMENT OF PHARMACOKINETICS AND ANTITUMOR-ACTIVITY AGAINST HUMAN HEPATOMA-CELL LINE BY USING ADRIAMYCIN-ENTRAPPED STEALTH LIPOSOMES

Preferential accumulation in the reticuloendothelial system is one of the major obstacles to the use of liposomes as a drug carrier for targ eting therapy. To reduce their uptake ganglioside GM1 was introduced i nto the components of conventional liposomes that had been used in our targeting experiments. Two types of such liposomes were prepared. Tis sue distribution studies on Adriamycin entrapped in bath types of lipo somes clearly indicated that the uptake of Adriamycin by liver and spl een decreased to the level comparable to that of free Adriamycin admin istration. By contrast, the level of Adriamycin in the serum remains h igh, and some increase was observed in the accumulation to the tumor. Furthermore, Adriamycin in these liposomes, which were conjugated with anti-alpha-fetoprotein (AFP) antibody, inhibited the growth of AFP-po sitive human hepatoma Li-7 more efficiently than free Adriamycin or Ad riamycin in antibody-conjugated conventional liposomes. (C) 1996 Wiley -Liss, Inc.