Isolation, physicochemical characterization and preclinical efficacy evaluation of soluble scleroglucan.

Abstract

Herein we describe the isolation, physicochemical characterization and preclinical evaluation of a water-soluble biologic response modifier extracted from Sclerotium glucanicum. Alkaline extraction of insoluble S. glucanicum exopolymers produced a soluble scleroglucan composed of a triple-helical beta-1,3-linked glucopyranose backbone with single beta-1,6-linked glucopyranosyl branches every third subunit. Scleroglucan has a weight average molecular mass of 1.56 x 10(6) Da, a weight average root mean square distance from the center of gravity of the molecule to its farthest elements of 51.8 nm, a polydispersity (weight-average molecular mass/number average molecular mass) of 1.83 and intrinsic viscosity of 3.081 dl/g. Scleroglucan (250 mg/kg, intravenously) stimulated in vivo murine macrophage phagocytic activity (66%, P less than .001) and increased in vitro macrophage tumor cytotoxicity against syngeneic tumor targets by 124% (P less than .05). Scleroglucan enhanced (P less than .001) murine bone marrow proliferation in a biphasic manner by up to 328%. Scleroglucan therapy increased survival of mice challenged with syngeneic lymphoma, melanoma or adenocarcinoma. AKR/J mice bearing syngeneic lymphoma (1 x 10(3) cells, intraperitoneally) demonstrated increased (P less than .001) long-term survival (100% vs. 0%, greater than 64 days). C57Bl/6J mice bearing syngeneic melanoma B16 (5 x 10(5) cells, subcutaneously) demonstrated increased long-term survival (64% vs. 0%, P less than .05). C57Bl/6J mice bearing syngeneic adenocarcinoma BW10232 (1 x 10(5) cells, subcutaneously) demonstrated increased (P less than .05) median survival time. In addition, scleroglucan prophylaxis increased resistance of mice to challenge with Staphylococcus aureus, Candida albicans and mouse hepatitis virus A-59. Scleroglucan did not induce toxicity or hepatomegaly. We conclude that: 1) a branched, water-soluble beta-1,3-linked scleroglucan biologic response modifier can be extracted from S. glucanicum; 2) scleroglucan will stimulate immunity, modify experimental neoplastic disease and increase resistance to microbial challenge; and 3) scleroglucan shows promise as an immunopotentiating drug.

• Authors: H A Pretus, H E Ensley, R B McNamee, E L Jones, I W Browder, D L Williams
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 257 Issue 1 Pg. 500-10 (Apr 1991) ISSN: 0022-3565 [Print] United States
• PMID: 1902259 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucans
• Immunologic Factors
• scleroglucan

Topics

• Animals
• Bone Marrow (drug effects)
• Candidiasis (drug therapy, pathology)
• Glucans (chemistry, isolation & purification, therapeutic use)
• Immunologic Factors (chemistry, isolation & purification, therapeutic use)
• Infection Control
• Magnetic Resonance Spectroscopy
• Male
• Mice
• Mice, Inbred AKR
• Mice, Inbred C57BL
• Molecular Conformation
• Molecular Weight
• Neoplasms, Experimental (drug therapy)
• Phagocytosis (drug effects)
• Viscosity