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Plasma lipoproteins as targeting carriers to tumour tissues after administraion of a lipophilic agent to mice
Author(s) -
Tokui Taro,
Kuroiwa Chitose,
Muramatsu Shigeki,
Tokui Yoko,
Sasagawa Kazuhiko,
Ikeda Toshihiko,
Komai Toru
Publication year - 1995
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510160204
Subject(s) - lipophilicity , chemistry , in vivo , albumin , lipoprotein , in vitro , pharmacology , serum albumin , endogeny , spleen , biochemistry , medicine , cholesterol , biology , microbiology and biotechnology
We synthesized 14 C‐warfarin hexadecyl ether ( 14 C‐WHE) by addition of a palmityl moiety to the hydroxyl group at the 4‐position of 14 C‐warfarin, a compound known to bind to serum albumin. 14 C‐WHE preferentially bound to the lipoproteins, low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL), in mouse plasma both in vitro and in vivo. 14 C‐Warfarin mainly concentrated in the liver immediately after intravenous administration to mice bearing M5076 sarcoma, and was found at only low concentrations in other tissues including the tumour. 14 C‐WHE highly distributed to the tumour, in other tissues including the tumour. 14 C‐WHE highly distributed to the tumour, adrenal, and spleen, as well as the liver. These tissues coincided with those in which human 125 I‐LDL was vigorously incorporated. The results indicate that chemical modification of an agent, giving it high lipophilicity, will enable it to bind to lipoproteins after intravenous administration. These modifications raise the possibility of lipoproteins as endogenous targeting carriers into tumour cells, which have high LDL‐receptor activity.