EFFECTS OF PH ON THE KINETICS OF THE INTERACTION BETWEEN ANTHRACYCLINES AND LIPID BILAYERS

In the present study we have analyzed the kinetics of the initial step s (first 10 seconds) of the interaction between the anthracycline daun omycin (DNM) and artificial lipid vesicles bearing opposite surface ch arge. The process can be monitored by measuring the fluorescence incre ase of the drug accompanying its association with the lipid bilayers. The results indicated that DNM consistently interacts to a larger exte nt with the liposomes having negative surface charge than with those h aving positive surface charge, suggesting the involvement of electrost atic components in the interaction. In contrast, DNM associates with t he vesicles bearing positive surface charge 2-3 times faster (in terms of the apparent rate constants describing the process of interaction) than with those having negative surface charge, an observation probab ly related to the more fluid physical state of the former. Regarding t he rate of access of DNM to the vesicles, rather than depending on the surface charge of the vesicles, this is critically affected by the io nization state of the drug, i.e. by the pH. Thus, the rate at which th e interaction proceeds is increased nearly 15-fold when the pH of the medium increases from 7.0 to 8.3, regardless of the surface charge of the liposomes. On this basis, and taking into account the fact that th e anthracyclines enter the cells by passive diffusion, possible effect s of pH on the transport of these drugs through the membranes of tumor cells are discussed.