Liposomes- and ethosomes-associated distamycins: a comparative study

The present paper presents a comparative study of liposomes and ethosomes behaviour as specialized delivery systems for distamycin A (DA) and two of its derivatives. Liposomes and ethosomes were prepared by classical methods, extruded through polycarbonate filters and characterized in term of dimensions, morphology and encapsulation efficiency. It was found that DA was associated to vesicles (either liposomes or ethosomes) around 16.0%, while both derivatives of DA showed a percentage of association around 80% in the case of liposomes and around 50% in the case of ethosomes. In vitro antiproliferative activity experiments, performed on cultured human and mouse leukemic cells, demonstrated that vesicles were able to increase the activity of both derivatives of DA. In addition, it was shown that the aging of both liposome- and ethosomes-associated distamycins suspensions did not heavily influence the vesicle size, whilst all samples showed a relevant drug leakage with time. Moreover, according to the different physico-chemical characteristics of DA and its derivatives (i.e. log P), vesicle-associated DA showed a highest loss of drug with respect to both its derivatives. In conclusion the enhancement of the drug activity through the delivery systems-associated DD could result in an efficient therapeutic effect by reducing or minimizing the toxic effects occurring during distamycins administration.