A Novel Injectable Water-Soluble Amphotericin B-Arabinogalactan Conjugate
- 1 August 1999
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 43 (8), 1975-1981
- https://doi.org/10.1128/aac.43.8.1975
Abstract
New, stable, highly water-soluble, nontoxic polysaccharide conjugates of amphotericin B (AmB) are described. AmB was conjugated by a Schiff-base reaction with oxidized arabinogalactan (AG). AG is a highly branched natural polysaccharide with unusual water solubility (70% in water). A high yield of active AmB was obtained with the conjugates which were similarly highly water soluble and which could be appropriately formulated for injection. They showed comparable MICs for Candida albicans and Cryptococcus neoformans (MICs, 0.1 to 0.2 μg/ml). The reduced AmB conjugate, which was synthesized at pH 11 for 48 h at 37°C, was nonhemolytic and was much safer than conventional micellar AmB-deoxycholate. It was the least toxic AmB-AG conjugate among those tested with mice (maximal tolerated dose, 50 mg/kg of body weight), and histopathology indicated no damage to the liver or kidneys. This conjugate, similarly to the liposomal formulation (AmBisome), was more effective than AmB-deoxycholate in prolonging survival. It was more effective than both the liposomal and the deoxycholate formulations in eradicating yeast cells from target organs. The overall results suggest that after further development of the AmB-AG conjugate, it may be a potent agent in the treatment of fungal infections.Keywords
This publication has 25 references indexed in Scilit:
- Lipid Formulations of Amphotericin B: Recent Progress and Future DirectionsClinical Infectious Diseases, 1996
- Psoralen-Containing Vinyl Monomer for Conjugation of Double-Helical DNA with Vinyl PolymersBioconjugate Chemistry, 1994
- Overview of amphotericin B colloidal dispersion (Amphocil)Journal of Infection, 1994
- Liposomal amphotericin B, AmBisomeJournal of Infection, 1994
- The enterococcus: a classic example of the impact of antimicrobial resistance on therapeutic optionsJournal of Antimicrobial Chemotherapy, 1991
- Amphotericin B: 30 Years of Clinical ExperienceClinical Infectious Diseases, 1990
- Amphotericin B NephrotoxicityDrug Safety, 1990
- Toxicity of Solubilized and Colloidal Amphotericin B Formulations to Human ErythrocytesJournal of Pharmacy and Pharmacology, 1988
- Infectious complications in the cancer patientCurrent Problems in Cancer, 1977
- Pharmacology, toxicity, and therapeutic usefulness of amphotericin BJAMA, 1966