Macromolecular carriers to enhance distamycins’ activity

Distamycins are compounds displaying antiviral, antibiotic and interesting antiprotozoal activity related to their ability to reversibly bind to the minor groove of DNA. In this study, we compared the performances of (a) liposomes and micellar systems to deliver A semi-synthetic distamycins and (b) liposomes and ethosomes as specialized delivery systems for benzo-heterocyclic distamycins. In the first case, the analysis of the in vitro antiproliferative activity on cultured human K562 and mouse L1210 leukemic cells demonstrated that liposomes and micellar solutions containing distamycins exert quite different effects as compared to that shown by the free drug depending on the type of drug and also of the cell line used. The activity of distamycins released by specialized delivery systems is in many cases higher with respect to the correspondent drug tested in the free form. In the second case, the analysis of the in vitro antiproliferative activity of distamycin A and its benzoheterocyclic derivatives on cultured human K562 and mouse leukemic L1210 cells demonstrated that the drugs administrated within vesicles are more effective than the corresponding free form used in the same conditions. The obtained results suggest that the enhancement of drug activity expressed by distamycins administrated by macromolecular carrier could reduce or minimize the toxicity occurring with high dosage of distamycins.