EQUILIBRIUM BINDING OF ANTHRACYCLINE CYTOSTATICS TO SERUM-ALBUMIN ANDSMALL UNILAMELLAR PHOSPHOLIPID-VESICLES AS MEASURED BY GEL-FILTRATION

A Sephadex G-200 gel filtration method was used to measure directly th e equilibrium binding of five important anthracycline analogs to serum albumin. The order of the overall binding constant (K) in a 150 mM Na Cl, 20 mM Hepes buffer (pH 7.45) was doxorubicin < daunorubicin < 4-de methoxydaunorubicin approximate to 13-dihydro-4'-deoxy-4'-iododoxorubi cin < 4'-deoxy-4'-iododoxorubicin for human serum albumin (K = 2.67 +/ - 0.07 mM(-1) to 24.5 +/- 3.1 mM(-1)) and bovine serum albumin (K = 1. 36 +/- 0.25 mM(-1) to 48.4 +/- 5.2 mM(-1)). Data were given on the pH- dependence of K. The anthracycline-albumin association reaction was co mpared with measurements of drug partitioning into unilamellar phospho lipid membranes and octanol. The results provide important new data re quired for a systematic kinetic analysis of anthracycline transport in tumor cells under serum conditions in a biological system. (C) 1998 E lsevier Science Inc.