Dextran is a complex branched

glucan A glucan is a polysaccharide derived from D-glucose, linked by glycosidic bonds. Glucans are noted in two forms: alpha glucans and beta glucans. Many beta-glucans are medically important. They represent a drug target for antifungal medications ...

(

polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with ...

derived from the condensation of

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, usi ...

), originally derived from

wine Wine is an alcoholic drink typically made from fermented grapes. Yeast consumes the sugar in the grapes and converts it to ethanol and carbon dioxide, releasing heat in the process. Different varieties of grapes and strains of yeasts are ...

IUPAC The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...

defines dextrans as "Branched poly-α-d-glucosides of microbial origin having glycosidic bonds predominantly C-1 → C-6". Dextran chains are of varying lengths (from 3 to 2000

kilodaltons The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at ...

). The polymer main chain consists of α-1,6 glycosidic linkages between glucose monomers, with branches from α-1,3 linkages. This characteristic branching distinguishes a dextran from a

dextrin Dextrins are a group of low-molecular-weight carbohydrates produced by the hydrolysis of starch and glycogen. Dextrins are mixtures of polymers of D-glucose units linked by α-(1→4) or α-(1→6) glycosidic bonds. Dextrins can be produced from ...

, which is a straight chain glucose polymer tethered by α-1,4 or α-1,6 linkages.

Occurrence

Dextran was discovered by

Louis Pasteur Louis Pasteur (, ; 27 December 1822 – 28 September 1895) was a French chemist and microbiologist renowned for his discoveries of the principles of vaccination, microbial fermentation and pasteurization, the latter of which was named after ...

as a microbial product in wine, but mass production was only possible after the development by Allene Jeanes of a process using

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...

Dental plaque Dental plaque is a biofilm of microorganisms (mostly bacteria, but also fungi) that grows on surfaces within the mouth. It is a sticky colorless deposit at first, but when it forms tartar, it is often brown or pale yellow. It is commonly found be ...

is rich in dextrans. Dextran is a complicating contaminant in the refining of sugar because it elevates the viscosity of

sucrose Sucrose, a disaccharide, is a sugar composed of glucose and fructose subunits. It is produced naturally in plants and is the main constituent of white sugar. It has the molecular formula . For human consumption, sucrose is extracted and refi ...

solutions and fouls plumbing. Dextran is now produced from sucrose by certain

lactic acid bacteria Lactobacillales are an order of gram-positive, low-GC, acid-tolerant, generally nonsporulating, nonrespiring, either rod-shaped ( bacilli) or spherical ( cocci) bacteria that share common metabolic and physiological characteristics. These bact ...

of the family lactobacillus. Species include '' Leuconostoc mesenteroides'' and '' Streptococcus mutans''. The structure of dextran produced depends not only on the family and species of the bacterium but on the strain. They are separated by fractional precipitation from protein-free extracts using

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a h ...

. Some bacteria coproduce fructans, which can complicate isolation of the dextrans.

Uses

Dextran 70 is on the

WHO Model List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

, the most important medications needed in a

health system Health, according to the World Health Organization, is "a state of complete physical, Mental health, mental and social well-being and not merely the absence of disease and infirmity".World Health Organization. (2006)''Constitution of the World H ...

. Medicinally it is used as an antithrombotic (anti

platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...

), to reduce blood

viscosity The viscosity of a fluid is a measure of its resistance to deformation at a given rate. For liquids, it corresponds to the informal concept of "thickness": for example, syrup has a higher viscosity than water. Viscosity quantifies the inte ...

, and as a volume expander in hypovolaemia.

Microsurgery

These agents are used commonly by microsurgeons to decrease vascular

thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thr ...

. The antithrombotic effect of dextran is mediated through its binding of

erythrocytes Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

platelets Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...

, and vascular

endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the ve ...

, increasing their

electronegativity Electronegativity, symbolized as , is the tendency for an atom of a given chemical element to attract shared electrons (or electron density) when forming a chemical bond. An atom's electronegativity is affected by both its atomic number and the ...

and thus reducing

erythrocyte Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

aggregation and

adhesiveness. Dextrans also reduce factor VIII-Ag

Von Willebrand factor Von Willebrand factor (VWF) () is a blood glycoprotein involved in hemostasis, specifically, platelet adhesion. It is deficient and/or defective in von Willebrand disease and is involved in many other diseases, including thrombotic thrombocytop ...

, thereby decreasing platelet function. Clots formed after administration of dextrans are more easily lysed due to an altered thrombus structure (more evenly distributed platelets with coarser

fibrin Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerize. The polymerized fibrin, together with pla ...

). By inhibiting α-2 antiplasmin, dextran serves as a

plasminogen Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encod ...

activator, so possesses

thrombolytic Thrombolysis, also called fibrinolytic therapy, is the breakdown (lysis) of blood clots formed in blood vessels, using medication. It is used in ST elevation myocardial infarction, stroke, and in cases of severe venous thromboembolism (massi ...

features. Outside of these features, larger dextrans, which do not pass out of the vessels, are potent osmotic agents, thus have been used urgently to treat

hypovolemia Hypovolemia, also known as volume depletion or volume contraction, is a state of abnormally low extracellular fluid in the body. This may be due to either a loss of both salt and water or a decrease in blood volume. Hypovolemia refers to the lo ...

. The hemodilution caused by volume expansion with dextran use improves blood flow, thus further improving patency of microanastomoses and reducing thrombosis. Still, no difference has been detected in antithrombotic effectiveness in comparison of intra-arterial and intravenous administration of dextran. Dextrans are available in multiple molecular weights ranging from 3 kDa to 2 MDa. The larger dextrans (>60,000 Da) are excreted poorly from the kidney, so remain in the blood for as long as weeks until they are metabolized. Consequently, they have prolonged antithrombotic and colloidal effects. In this family, dextran-40 (MW: 40,000 Da), has been the most popular member for

anticoagulation Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where they ...

therapy. Close to 70% of dextran-40 is excreted in urine within the first 24 hours after intravenous infusion, while the remaining 30% are retained for several more days.

Other medical uses

* Dextran is used in some

eye drop Eye drops or eyedrops are liquid drops applied directly to the surface of the eye usually in small amounts such as a single drop or a few drops. Eye drops usually contain saline to match the salinity of the eye. Drops containing only saline an ...

s as a lubricant. and in certain intravenous fluids to solubilize other factors, such as iron (in a solution known as Iron Dextran). * Intravenous solutions with dextran function both as volume expanders and means of

parenteral nutrition Parenteral nutrition (PN) is the feeding of nutritional products to a person intravenously, bypassing the usual process of eating and digestion. The products are made by pharmaceutical compounding companies. The person receives a nutritional m ...

. Such a solution provides an osmotically neutral fluid that once in the body is digested by cells into glucose and free water. It is occasionally used to replace lost

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in th ...

in emergency situations, when replacement blood is not available, but must be used with caution as it does not provide necessary electrolytes and can cause

hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be a ...

or other electrolyte disturbances. * Dextran also increases

blood sugar Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...

levels. * Dextran can be used in an ATPS for PEGylation

Laboratory uses

* Dextran is used in the

osmotic stress technique The osmotic stress technique is a method for measuring the effect of water on biological molecules, particularly enzymes. Just as the properties of molecules can depend on the presence of salts, pH, and temperature, they can depend significantly o ...

for applying

osmotic pressure Osmotic pressure is the minimum pressure which needs to be applied to a solution to prevent the inward flow of its pure solvent across a semipermeable membrane. It is also defined as the measure of the tendency of a solution to take in a pure ...

to biological molecules. * It is also used in some size-exclusion

chromatography In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system ( ...

matrices; an example is

Sephadex Sephadex is a cross-linked dextran gel used for gel filtration. It was launched by Pharmacia in 1959, after development work by Jerker Porath and Per Flodin. The name is derived from separation Pharmacia dextran. It is normally manufactured i ...

. * Dextran has also been used in bead form to aid in

bioreactor A bioreactor refers to any manufactured device or system that supports a biologically active environment. In one case, a bioreactor is a vessel in which a chemical process is carried out which involves organisms or biochemically active substances ...

applications. * Dextran has been used as an immobilization agent in biosensors. * Dextran preferentially binds to early endosomes;

fluorescent Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, th ...

-labelled dextran can be used to visualize these endosomes under a

microscope A microscope () is a laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic means being invisibl ...

. * Dextran can be used as a stabilizing coating to protect metal

nanoparticles A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 10 ...

from

oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...

and improve

biocompatibility Biocompatibility is related to the behavior of biomaterials in various contexts. The term refers to the ability of a material to perform with an appropriate host response in a specific situation. The ambiguity of the term reflects the ongoing de ...

. * Dextran coupled with a fluorescent molecule such as

fluorescein isothiocyanate Fluorescein isothiocyanate (FITC) is a derivative of fluorescein used in wide-ranging applications including flow cytometry. First described in 1942, FITC is the original fluorescein molecule functionalized with an isothiocyanate reactive group ...

can be used to create concentration gradients of diffusible molecules for imaging and allow subsequent characterization of gradient slope. * Solutions of fluorescently-labelled dextran can be perfused through engineered vessels to analyze

vascular permeability Vascular permeability, often in the form of capillary permeability or microvascular permeability, characterizes the capacity of a blood vessel wall to allow for the flow of small molecules (drugs, nutrients, water, ions) or even whole cells ( lymp ...

* Dextran is used to make

microcarriers A microcarrier is a support matrix that allows for the growth of adherent cells in bioreactors. Instead of on a flat surface, cells are cultured on the surface of spherical microcarriers so that each particle carries several hundred cells, and the ...

for industrial cell culture * Orally-administered

dextran sodium sulphate Dextran is a complex branched glucan (polysaccharide derived from the condensation of glucose), originally derived from wine. IUPAC defines dextrans as "Branched poly-α-d-glucosides of microbial origin having glycosidic bonds predominantly C- ...

is used to induce

colitis Colitis is swelling or inflammation of the large intestine ( colon). Colitis may be acute and self-limited or long-term. It broadly fits into the category of digestive diseases. In a medical context, the label ''colitis'' (without qualification ...

in animal models of

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine and large intestine, as wel ...

Side effects

Although relatively few side effects are associated with dextran use, these side effects can be very serious. These include

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...

, volume overload,

pulmonary edema Pulmonary edema, also known as pulmonary congestion, is excessive liquid accumulation in the tissue and air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia and respiratory failure. It is du ...

cerebral edema Cerebral edema is excess accumulation of fluid (edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compressio ...

, or platelet dysfunction. An uncommon but significant complication of dextran osmotic effect is

acute kidney injury Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both. Causes of AKI are cl ...

. The pathogenesis of this kidney failure is the subject of many debates with direct toxic effect on tubules and

glomerulus ''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn". ''Glomerulus'' may refer to: * the filter ...

versus intraluminal hyperviscosity being some of the proposed mechanisms. Patients with history of

diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

chronic kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, ...

, or vascular disorders are most at risk. Brooks and others recommend the avoidance of dextran therapy in patients with chronic kidney disease.

Research

Efforts have been made to develop modified dextran polymers. One of these has

acetal In organic chemistry, an acetal is a functional group with the connectivity . Here, the R groups can be organic fragments (a carbon atom, with arbitrary other atoms attached to that) or hydrogen, while the R' groups must be organic fragment ...

modified

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydrox ...

groups. It is

insoluble In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solub ...

in water, but soluble in organic

solvents A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...

. This allows it to be processed in the same manner as many polyesters, like poly(lactic-co-glycolic acid), through processes like solvent evaporation and

emulsion An emulsion is a mixture of two or more liquids that are normally immiscible (unmixable or unblendable) owing to liquid-liquid phase separation. Emulsions are part of a more general class of two-phase systems of matter called colloids. Althou ...

Acetalated dextran Acetalated dextran is a biodegradable polymer based on dextran that has acetal modified Hydroxy group, hydroxyl groups. After synthesis, the Hydrophile, hydrophilic polysaccharide dextran is rendered Solubility, insoluble in water, but soluble in ...

is structurally different from acetylated dextran. As of 2017 several uses for drug delivery had been explored ''in vitro'' and a few had been tested in animal models.

References

External links

Resource on dextran properties and structure of dextran polymers
* {{Blood substitutes and perfusion solutions Biotechnology products Polysaccharides Intravenous fluids