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In Polysaccharides for Drug Delivery and Pharmaceutical Applications; Marchessault, R., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2006.
264
The term "levan" was introduced over 100 years ago to describe the
exopolysaccharide produced by a Bacillus when grown on sucrose (I). While
the glucose portion of the substrate is used as a microbial energy source, the
fructose units are linked together to build levan, a natural polymer of fructose.
β-D-fructo-furanosyl residues are connected by β-2,6 linkages. Branching is
accomplished through occasional β-2,1 bonds. The degree of branching varies
with the organism used in production but has been reported as high as 20%.
Several dozen bacteria are known to produce levan, including species of
Acetobacter, Aerobacter, Azotobacter, Bacillus, Corynebacterium, Erwinia,
Gluconobacter, Mycobacterium, Pseudomonas, Streptococcus, and Zymomonas
(1,2). The molecular weights of microbial levans are usually greater than 0.5
million and occasionally as high as 40 million (3). Levans made by plants are
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Properties of Levan
Adhesive
Levan is water soluble but does not swell in water. It has potential use in
bonding of tablets when dissolution is desired shortly after ingestion. If a more
gradual breakup of the tablet is desired, a more water resistant fructan would be
useful. Indeed, there is another fructan with low water solubility. This fructan,
inulin, is chemically identical to levan, but bonding through the 2 and 1 carbons
(as opposed to the 2 and 6 carbons of levan) results in a largely water insoluble
compound. However, the adhesive strength of inulin is only about one-tenth that
of levan.
Although there are numerous methods for decreasing the water solubility of
a material, the moieties responsible for the adhesive properties of levan are also
In Polysaccharides for Drug Delivery and Pharmaceutical Applications; Marchessault, R., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2006.
265
responsible for the interaction with water. Numerous attempts were required to
solve the dilemma. Ultimately, a cross-linking procedure was found to be the
most successful. The formulation is being optimized and will be published in the
near future.
Spherical Shape
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Publication Date: June 22, 2006 | doi: 10.1021/bk-2006-0934.ch013
Membrane Protection
In Polysaccharides for Drug Delivery and Pharmaceutical Applications; Marchessault, R., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2006.
266
Film Formation
Levan can be readily formed into a film. Not allowing the film to
completely dry by adding a small amount of plasticizer will keep the film
flexible. Mixing levan with another polysaccharide, curdlan, will also result in a
flexible film. Perhaps more unexpected, was the result of mixing levan with the
clay, montmorillonite. One part of montmorillonite was mixed with either 2 or 5
parts of levan. A flexible film was formed. The surprise was that the film was
water resistant. These properties suggest potential application as a flexible
coating or bandage. For a natural material, levan is quite heat stable with a
melting point of 225 °C. Although autoclave moisture will interfere with pre-
formed bonds, once excess moisture is removed, the levan regains its adhesive
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strength.
Publication Date: June 22, 2006 | doi: 10.1021/bk-2006-0934.ch013
Calcium Absorption
Lowering Cholesterol
Ishihara was among the first to establish the value of high molecular weight
levan as a hypocholesterolemic agent. He found that high molecular weight
In Polysaccharides for Drug Delivery and Pharmaceutical Applications; Marchessault, R., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2006.
267
Additional Applications
Levan has long been known to be an antitumor agent (12, 17, 18). Multiple
mechanisms have been attributed to this activity. The host immune response is
modulated, there is a direct inhibitory effect on tumor cells and levan augments
the activity of other antitumor compounds (17,19). Administration of fructans
has been shown to reduce the incidence of carcinogen-induced pre-cancerous
lesions in rats (20).
In Polysaccharides for Drug Delivery and Pharmaceutical Applications; Marchessault, R., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2006.
268
Like dextran, levan can be used to create two phase liquid systems, of
potential value in purification of biological materials (5).
Garegg et. al. tested high molecular weight levan derivatives and found a
number of potential applications. For example, in an assay for inhibition of
smooth muscle cell proliferation, the activity of the levan sulfate was one log
greater than for the commercial heparin used for comparison. They also found
levan sulfate effective in reducing virus growth in an in vitro test. Phosphated
levan caused water and certain solvents to gel. Suggested uses for this gelled
form of levan were in pharmaceuticals and as a fat substitute (27).
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Conclusions
Publication Date: June 22, 2006 | doi: 10.1021/bk-2006-0934.ch013
Acknowledgement
References
In Polysaccharides for Drug Delivery and Pharmaceutical Applications; Marchessault, R., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2006.
269
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In Polysaccharides for Drug Delivery and Pharmaceutical Applications; Marchessault, R., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2006.