Conjugation of amino-containing drugs to polysaccharides by tosylation: amphotericin B-arabinogalactan conjugates

The coupling of amphotericin-B (AmB), a water-insoluble antifungal and antileishmanial agent, to arabinogalactan (AG) via tosylate or mesylate derivatives was investigated as a method for the conjugation of amino-containing drugs to polysaccharides. in the first step, AG was reacted with tosyl- or mesyl-chloride at different ratios to obtain tosylate or mesylate AG derivatives. AmB was conjugated to AG derivatives in either aqueous or organic media via an amine bond. AG-AmB conjugates were soluble in water and exhibited improved stability in aqueous solutions as compared to the unbound drug. The conjugates showed comparable inhibitory concentration values against the pathogenic yeast Candida albicans, and against Leishmania major parasites. They were about 60 times less hemolytic against sheep erythrocytes than the free drug, and less toxic when injected i.v. to BALB/c mice. (C) 2003 Elsevier Ltd. All rights reserved.