DEVELOPMENT, PHYSICOCHEMICAL CHARACTERIZATION AND PRECLINICAL EFFICACY EVALUATION OF A WATER-SOLUBLE GLUCAN SULFATE DERIVED FROM SACCHAROMYCES-CEREVISIAE

This report describes the development, characterization and preclinical efficacy evaluation of water soluble glucan sulfate. Glucan sulfate was derived from insoluble beta-1,3-D-glucan isolated from Saccharomyces cerevisiae. The proposed repeating unit empirical formula of glucan sulfate is [(C6H10O5)5.3H2SO4]n. Two polymer peaks were resolved by aqueous high-performance size exclusion chromatography (HPSEC) with on-line multi-angle laser light scattering (MALLS) photometry and differential viscometry. Peak 1 (M(w) = 1 219 697 Da) represents almost-equal-to 1% of the total polymers, while peak 2 (M(w) = 8 884 Da) accounts for almost-equal-to 99% of polymers. C-13-NMR spectroscopy suggests that glucan sulfate polymer strands may be partially cross-linked. Glucan sulfate (250 mg/kg, i.v.) increased (P < 0.01) macrophage vascular clearance of I-131-reticuloendothelial emulsion by 42% (P < 0.01) and in vitro bone marrow proliferation by 46% (P < 0.05). Glucan sulfate (250 mg/kg, i.v.) increased (P < 0.05) median survival time of C57B1/6J mice with syngeneic melanoma B16 or sarcoma M5076. In addition, glucan sulfate immunoprophylaxis increased resistance of mice to challenge with Escherichia coli, Candida albicans or Mouse Hepatitis Virus strain A-59. We concluded that: (1) insoluble beta-1,3-D-glucan can be converted to a water soluble sulfated form; (2) glucan sulfate activates macrophages and stimulates bone marrow; (3) glucan sulfate exerts antitumor therapeutic activity, and (4) glucan sulfate immunoprophylaxis will modify the course of experimental infectious disease.