Chitosan is a linear polysaccharide composed of randomly distributed β-(1-4)-linked D-glucosamine
and N-acetyl-D-glucosamine. It is made by treating shrimp and other crustacean shells
with the alkali sodium hydroxide. Chitosan has a number of commercial and possible
biomedical uses. It can be used in agriculture as a seed treatment and biopesticide, helping
plants to fight off fungal infections. In winemaking it can be used as a fining agent,
also helping to prevent spoilage. In industry, it can be used in a self-healing polyurethane
paint coating. In medicine, it may be useful in bandages to reduce bleeding and as an antibacterial
agent; it can also be used to help deliver drugs through the skin.
More controversially, chitosan has been asserted to have use in limiting fat absorption, which
would make it useful for dieting, but there is evidence against this.
Other uses of chitosan that have been researched include use as a soluble dietary fiber.
Manufacture and properties
Chitosan is produced commercially by deacetylation of chitin, which is the structural element
in the exoskeleton of crustaceans and cell walls of fungi. The degree of deacetylation
can be determined by NMR spectroscopy, and the %DD in commercial chitosans ranges from
60 to 100%. On average, the molecular weight of commercially produced chitosan is between
3800 and 20,000 Daltons. A common method for the synthesis of chitosan is the deacetylation
of chitin using sodium hydroxide in excess as a reagent and water as a solvent. This
reaction pathway, when allowed to go to completion yields up to 98% product.
The amino group in chitosan has a pKa value of ~6.5, which leads to a protonation in acidic
to neutral solution with a charge density dependent on pH and the %DA-value. This makes
chitosan water soluble and a bioadhesive which readily binds to negatively charged surfaces
such as mucosal membranes. Chitosan enhances the transport of polar drugs across epithelial
surfaces, and is biocompatible and biodegradable. It is not approved by FDA for drug delivery
though. Purified quantities of chitosans are available for biomedical applications.
Chitosan and its derivatives, such as trimethylchitosan, have been used in nonviral gene delivery.
Trimethylchitosan, or quaternised chitosan, has been shown to transfect breast cancer
cells, with increased degree of trimethylation increasing the cytotoxicity; at approximately
50% trimethylation, the derivative is the most efficient at gene delivery. Oligomeric
derivatives are relatively nontoxic and have good gene delivery properties.
Usage Agricultural and horticultural use
The agricultural and horticultural uses for chitosan, primarily for plant defense and
yield increase, are based on how this glucosamine polymer influences the biochemistry and molecular
biology of the plant cell. The cellular targets are the plasma membrane and nuclear chromatin.
Subsequent changes occur in cell membranes, chromatin, DNA, calcium, MAP Kinase, oxidative
burst, reactive oxygen species, callose pathogenesis-related genes and phytoalexins.
Natural biocontrol and elicitor In agriculture, chitosan is used primarily
as a natural seed treatment and plant growth enhancer, and as an ecologically friendly
biopesticide substance that boosts the innate ability of plants to defend themselves against
fungal infections. The natural biocontrol active ingredients, chitin/chitosan, are found
in the shells of crustaceans, such as lobsters, crabs, and shrimp, and many other organisms,
including insects and fungi. It is one of the most abundant biodegradable materials
in the world. Degraded molecules of chitin/chitosan exist
in soil and water. Chitosan applications for plants and crops are regulated by the EPA,
and the USDA National Organic Program regulates its use on organic certified farms and crops.
EPA-approved, biodegradable chitosan products are allowed for use outdoors and indoors on
plants and crops grown commercially and by consumers.
The natural biocontrol ability of chitosan should not be confused with the effects of
fertilizers or pesticides upon plants or the environment. Chitosan active biopesticides
represent a new tier of cost-effective biological control of crops for agriculture and horticulture.
The biocontrol mode of action of chitosan elicits natural innate defense responses within
plant to resist insects, pathogens, and soil-borne diseases when applied to foliage or the soil.
Chitosan increases photosynthesis, promotes and enhances plant growth, stimulates nutrient
uptake, increases germination and sprouting, and boosts plant vigor. When used as seed
treatment or seed coating on cotton, corn, seed potatoes, soybeans, sugar beets, tomatoes,
wheat and many other seeds, it elicits an innate immunity response in developing roots
which destroys parasitic cyst nematodes without harming beneficial nematodes and organisms.
Agricultural applications of chitosan can reduce environmental stress due to drought
and soil deficiencies, strengthen seed vitality, improve stand quality, increase yields, and
reduce fruit decay of vegetables, fruits and citrus crops. Horticultural application of
chitosan increases blooms and extends the life of cut flowers and Christmas trees. The
US Forest Service has conducted research on chitosan to control pathogens in pine trees
and increase resin pitch outflow which resists pine beetle infestation.
Chitosan has a rich history of being researched for applications in agriculture and horticulture
dating back to the 1980s. By 1989, chitosan salt solutions were applied to crops for improved
freeze protection or to crop seed for seed priming. Shortly thereafter, chitosan salt
received the first ever biopesticide label from the EPA, then followed by other intellectual
property applications. Chitosan has been used to protect plants in
space, as well, exemplified by NASA's experiment to protect adzuki beans grown aboard the space
shuttle and Mir space station in 1997. NASA results revealed chitosan induces increased
growth and pathogen resistance due to elevated levels of beta 1-3 glucanase enzymes within
plant cells. NASA confirmed chitosan elicits the same effect in plants on earth.
Nontoxic, low molecular weight chitosan polymer solutions appear to be safe enough for broad-spectrum
agricultural and horticultural uses. In 2008, the EPA approved natural broad-spectrum elicitor
status for an ultralow molecular active ingredient of 0.25% chitosan.
A natural chitosan elicitor solution for agriculture and horticultural uses was granted an amended
label for foliar and irrigation applications by the EPA in 2009. Given its low potential
for toxicity and abundance in the natural environment, chitosan does not harm people,
pets, wildlife, or the environment when used according to label directions. The US Forest
Service tested chitosan as an ecofriendly biopesticide to prearm pine trees to defend
themselves against mountain pine beetles. Water filtration
Chitosan can also be used in water processing engineering as a part of a filtration process.
Chitosan causes the fine sediment particles to bind together, and is subsequently removed
with the sediment during sand filtration. It also removes phosphorus, heavy minerals,
and oils from the water. Chitosan is an important additive in the filtration process. Sand filtration
apparently can remove up to 50% of the turbidity alone, while the chitosan with sand filtration
removes up to 99% turbidity. Chitosan has been used to precipitate caseins from bovine
milk and cheese making. Chitosan is also useful in other filtration
situations, where one may need to remove suspended particles from a liquid. In combination with
bentonite, gelatin, silica gel, isinglass, or other fining agents, it is used to clarify
wine, mead, and beer. Added late in the brewing process, chitosan improves flocculation, and
removes yeast cells, fruit particles, and other detritus that cause hazy wine. Chitosan
combined with colloidal silica is becoming a popular fining agent for white wines, because
chitosan does not require acidic tannins with which to flocculate.
Manufacture
Bioinspired materials, a manufacturing concept inspired by natural nacre, shrimp carapace
or insect cuticles, has led to development of methods to manufacture large scale consumer
objects using chitosan. This method is based on replicating the molecular arrangement of
chitosan from natural materials into fabrication methods, such as injection molding or mold
casting. Once discarded, chitosan-constructed objects are biodegradable and non-toxic. The
method is being explored to engineer human organs or tissues using three-dimensional
bioprinting. Pigmented chitosan objects can be recycled,
with the option of reintroducing or discarding the dye at each recycling step, enabling reuse
of the polymer independently of colorants. Unlike other plant-based bioplastics, the
main natural sources of chitosan are from marine environments and do not compete for
land or other human resources. The fabrication of large objects with chitosan
applies concepts from Shrilk, a chitosan material that replicates insect cuticle and a fibroin
protein from silk for uses in bioengineering. Winemaking and fungal source chitosan
Chitosan has a long history for use as a fining agent in winemaking. Fungal source chitosan
has shown an increase in settling activity, reduction of oxidized polyphenolics in juice
and wine, chelation and removal of copper and control of the spoilage yeast Brettanomyces.
These products and uses are approved for European use by the EU and OIV standards.
Potential industrial uses Scientists have developed a polyurethane coating
that heals its own scratches when exposed to sunlight. The self-healing coating uses
chitosan incorporated into traditional polymer materials, such as those used in coatings
on cars to protect paint. When a scratch damages the chemical structure, the chitosan responds
to sunshine by forming chemical chains that bond with other materials in the substance,
eventually smoothing the scratch. The process can take less than an hour.
The polymer can only repair itself in the same spot once, and would not work after repeated
scratches. Whether this technology can be applied to industrial materials, however,
depends on a number of factors, such as long-term persistence of the repair, stiffness and heat
resistance of the coating. Biomedical uses
Chitosan's properties allow it to rapidly clot blood, and has recently gained approval
in the United States and Europe for use in bandages and other hemostatic agents. Chitosan
hemostatic products have been shown in testing by the U.S. Marine Corps to quickly stop bleeding
and to reduce blood loss, and result in 100% survival of otherwise lethal arterial wounds
in swine. Chitosan hemostatic products reduce blood loss in comparison to gauze dressings
and increase patient survival. Chitosan hemostatic products have been sold to the U.S. Army and
are currently used by the UK military. Both the US and UK have already used the bandages
on the battlefields of Iraq and Afghanistan. Chitosan is hypoallergenic and has natural
antibacterial properties, which further support its use in field bandages.
Chitosan hemostatic agents are often chitosan salts made from mixing chitosan with an organic
acid. The hemostatic agent works by an interaction between the cell membrane of erythrocytes
and the protonated chitosan leading to involvement of platelets and rapid thrombus formation.
The chitosan salts can be mixed with other materials to make them more absorbent, or
to vary the rate of solubility and bioabsorbability of the chitosan salt. The chitosan salts are
biocompatible and biodegradable making them useful as absorbable haemostats. The protonated
chitosan is broken down by lysozyme in the body to glucosamine and the conjugate base
of the acid are substances naturally found in the body. The chitosan salt may be placed
on an absorbable backing. The absorbable backing may be synthetic or natural.
Chitosan's properties also allow it to be used in transdermal drug delivery; it is mucoadhesive
in nature, reactive, and most importantly, has a positive charge under acidic conditions.
This positive charge comes from protonation of its free amino groups. Lack of a positive
charge means chitosan is insoluble in neutral and basic environments. However, in acidic
environments, protonation of the amino groups leads to an increase in solubility. The implications
of this are very important to biomedical applications. This molecule will maintain its structure
in a neutral environment, but will solubilize and degrade in an acidic environment. This
means chitosan can be used to transport a drug to an acidic environment, where the chitosan
packaging will then degrade, releasing the drug to the desired environment. One example
of this drug delivery has been the transport of insulin.
Preliminary research and FDA review Supposed to limit fat absorption in the body,
chitosan may be sold in tablet form as a "fat binder". A Cochrane meta-analysis, which evaluated
clinical trials performed with dietary chitosan over a minimum of four weeks, body weight,
blood pressure and parameters related to cholesterol were changed only in some low-quality trials,
indicating a minor effect on body weight. Other higher quality trials indicated no significant
effect of chitosan and no clinical justification for advising overweight patients to take chitosan
supplements. In an experimental model of the digestive
tract, chitosan was shown to interact with oil, which inhibited duodenal absorption and
enhanced lipid excretion. However, the mechanism of interaction between chitosan and fat is
not well understood and has not been proved clinically. In mice, dietary ingestion of
chitosan did not depress the level of iron, zinc or copper.
The U.S. Food and Drug Administration has issued warning letters to supplement retailers
who made inappropriate claims about the supposed health benefits of using chitosan.
Chitosan is under research for several potential dietary or clinical applications:
As a soluble dietary fiber, it may increase gastrointestinal lumen viscosity and retard
emptying of the stomach, creating a sense of satiety.
It alters bile acid composition, increasing the excretion of sterols and reducing the
digestibility of ileal fats. It is unclear how chitosan does this, but the currently
favored hypotheses involve the increase of intestinal viscosity or bile acid-binding
capacity. Chitosan is relatively insoluble in water,
but can be dissolved by dilute acids, which would make it a highly-viscous dietary fiber.
Such fibers might inhibit the uptake of dietary lipids by increasing the thickness of the
boundary layer of the intestinal lumen, which has been observed in animal experiments.
Having very few acetyl groups, chitosan contains cationic groups. This may cause chitosan to
have bile acid-binding capacity, which causes mixed micelles to be entrapped or disintegrated
in the duodenum and ileum. This would interrupt bile acid circulation, causing reduced lipid
absorption and increased sterol excretion, which has also been observed in animal experiments.
See also Chitin
References
External links WebMD: Chitosan
Is Chitosan a "Fat Magnet"? — Quackwatch: A critical look on the claims how chitosan
can be used for weight management