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

Tirsta Ehrenfreund-Kleinman, Jacob Golenser, Abraham J. Domb

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3049-3057
Number of pages9
JournalBiomaterials
Volume25
Issue number15
DOIs
StatePublished - Jul 2004
Externally publishedYes

Bibliographical note

Funding Information:
We thank the Canadian Faye Kaufman foundation for their generous support. This work was supported in part by the Israel Academy of Science.We thank Rama Falk, and Dr. Zulma Gazit for their help with the in vivo experiments, and Tony Azzam for his technical help.

Funding

We thank the Canadian Faye Kaufman foundation for their generous support. This work was supported in part by the Israel Academy of Science.We thank Rama Falk, and Dr. Zulma Gazit for their help with the in vivo experiments, and Tony Azzam for his technical help.

FundersFunder number
Israel Academy of Science.We thank Rama Falk

    Keywords

    • Amphotericin-B
    • Arabinogalactan
    • Mesylate
    • Tosylate
    • Water-soluble conjugate

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