PHYSICOCHEMICAL PROPERTIES OF THE HEAT-INDUCED SUPERAGGREGATES OF AMPHOTERICIN-B

The aggregation state of amphotericin B (AmB) was previously reported to modulate its therapeutic efficiency. As a preliminary study to test the biological effects of 'superaggregates' generated by heat treatme nt, we present spectroscopic data related to their formation in aqueou s solutions. Drastic changes in the AmB aggregation state in water wer e shown to occur on heating at 50-60 degrees C, The concentration of t he aggregates formed at high (A(t)) or room (A) temperature, and the c oncentration of the monomeric form (M) of AmB were calculated by proce ssing absorption data, The thermally induced conversion from A to A(t) depends on the AmB concentration. Rayleigh scattering measurements su ggest that the A(t) aggregates are larger than the A aggregates, At ro om temperature, the condensation rate of A with M-leading to the 'supe raggregated' form A(t)-was slower and depended on the concentration of M. The superaggregated species A(t) was shown to be the most chemical ly stable species, Physico-chemical properties of these superaggregate s are discussed as a potential new solution to improve the therapeutic efficacy of AmB.