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 targeting therapy. To reduce their uptake, ganglioside GM1 was introduced into the components of conventional liposomes that had been used in our targeting experiments. Two types of such liposomes were prepared. Tissue distribution studies on Adriamycin entrapped in both types of liposomes clearly indicated that the uptake of Adriamycin by liver and spleen decreased to the level comparable to that of free Adriamycin administration. By contrast, the level of Adriamycin in the serum remains high, 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-positive human hepatoma Li-7 more efficiently than free Adriamycin or Adriamycin in antibody-conjugated conventional liposomes.
Shimizu
H
H
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Kumai
K
K
Uyama
I
I
Shibata
S
S
Tagawa
T
T
Nagaike
K
K
Yasuda
T
T
Kitajima
M
M
Tadakuma
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008081:Liposomes; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D013997:Time Factors; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D004317:Doxorubicin