View source for Dextran

{{distinguish|Dextrin}}
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|Section2={{Chembox Properties
| Formula = H(C<sub>6</sub>H<sub>10</sub>O<sub>5</sub>)<sub>x</sub>OH
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'''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-1 → C-6".<ref>{{cite book|chapter-url=https://goldbook.iupac.org/html/D/D01655.html|chapter=dextrans|doi=10.1351/goldbook.D01655|title=The IUPAC Compendium of Chemical Terminology|year=2014}}</ref> Dextran chains are of varying lengths (from 3 to 2000 [[Atomic mass unit|kilodaltons]]).

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]], which is a straight chain glucose polymer tethered by α-1,4 or α-1,6 linkages.<ref>{{cite journal|journal=Adv. Polym. Sci. |year=2006|volume=205|pages=199–291|doi=10.1007/12_100|title=Functional Polymers Based on Dextran|author1=Thomas Heinze |author2=Tim Liebert |author3=Brigitte Heublein |author4=Stephanie Hornig|series=Advances in Polymer Science|isbn=978-3-540-37102-1}}</ref>   <!-- (For information on the numbering of [[carbon]] [[atom]]s in glucose, see the [[glucose]] article.) -->

==Occurrence==
Dextran was discovered by [[Louis Pasteur]] as a microbial product in wine,<ref name=pasteur>{{cite journal | last = Pasteur|first= L. | title = On the viscous fermentation and the butyrous fermentation | journal = [[Bulletin de la Société Chimique de France|Bull. Soc. Chim. Paris]] |issn= 	0037-8968|language = fr| volume = 11 | pages = 30–31 | year = 1861}}</ref> but mass production was only possible after the development by [[Allene Jeanes]] of a process using [[bacteria]].<ref name="Human"/> [[Dental plaque]] is rich in dextrans.<ref>{{cite journal | pmc = 422963 | pmid=4594114 | volume=8 | title=Detection and preliminary studies on dextranase-producing microorganisms from human dental plaque | year=1973 | journal=Infect. Immun. | pages=1009–16 |vauthors=Staat RH, Gawronski TH, Schachtele CF | issue=6 | doi=10.1128/IAI.8.6.1009-1016.1973 }}</ref>  Dextran is a complicating contaminant in the refining of sugar because it elevates the viscosity of [[sucrose]] solutions and fouls plumbing.<ref name=Sidebotham>{{cite journal|journal=Adv. Carbohydr. Chem. Biochem.|year=1974|volume=30|pages=371–444|title=Dextrans|author=Sidebotham, R. L.|series=Advances in Carbohydrate Chemistry and Biochemistry|doi=10.1016/s0065-2318(08)60268-1|pmid=4157174|isbn=9780120072309}}</ref>

Dextran is now produced from sucrose by certain [[lactic acid bacteria]] 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]].  Some bacteria coproduce [[fructan]]s, which can complicate isolation of the dextrans.<ref name=Sidebotham/>

==Uses==
[[Dextran 70]] is on the [[WHO Model List of Essential Medicines]], the most important medications needed in a [[health system]].<ref name=WHO2015E>{{cite web |url=https://www.who.int/medicines/publications/essentialmedicines/EML2015_8-May-15.pdf |title=19th WHO Model List of Essential Medicines (April 2015) |date=April 2015 |access-date=May 10, 2015 |publisher=WHO }}</ref>

Medicinally it is used as an [[Thrombosis|antithrombotic]] (anti[[platelet]]), to reduce blood [[viscosity]], and as a volume expander in [[hypovolaemia]].<ref>{{cite book | title = Medical Surgical Nursing | edition = 8th  | last = Lewis|first=Sharon L. | year = 2010| publisher = Elsevier - Health Sciences Division |isbn= 978-0323079150}}</ref>

=== Microsurgery ===
These agents are used commonly by microsurgeons to decrease vascular [[thrombosis]]. The antithrombotic effect of dextran is mediated through its binding of [[erythrocytes]], [[platelets]], and vascular [[endothelium]], increasing their [[electronegativity]] and thus reducing [[erythrocyte]] aggregation and [[platelet]] adhesiveness. Dextrans also reduce factor VIII-Ag [[Von Willebrand factor]], 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]]{{Citation needed|reason=this fact should be cited somewhere, it is too interesting to leave without reference|date=May 2013}}). By inhibiting α-2 antiplasmin, dextran serves as a [[plasminogen]] activator, so possesses [[thrombolytic]] 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]] {{Citation needed|reason=missing reference|date=February 2022}}. 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 [[Anticoagulant|anticoagulation]] 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]]s as a lubricant.<ref>{{cite web|url=http://www.medicines.org.uk/EMC/medicine/74/SPC/Tears+Naturale/#CLINICAL_PARTS|title=Tears Naturale - Summary of Product Characteristics (SmPC) - (eMC)|website=www.medicines.org.uk}}</ref> and in certain intravenous fluids to solubilize other factors, such as iron (in a solution known as Iron Dextran).
*[[Intravenous therapy|Intravenous solution]]s with dextran function both as [[volume expander]]s and means of [[parenteral nutrition]]. 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]] in emergency situations, when replacement blood is not available,<ref name="Human">{{cite web|title=Allene Rosalind Jeanes|url=http://humantouchofchemistry.com/allene-rosalind-jeanes.htm|publisher=Human Touch of Chemistry|access-date=13 May 2014|url-status=dead|archive-url=https://web.archive.org/web/20140514101724/http://humantouchofchemistry.com/allene-rosalind-jeanes.htm|archive-date=14 May 2014}}</ref><ref name=Ogilvie>{{cite book|last1=Ogilvie|first1=Marilyn|last2=Harvey|first2=Joy|author-link1=Marilyn Bailey Ogilvie|author-link2=Joy Harvey|title=The biographical dictionary of women in science|url=https://archive.org/details/biographicaldict00ogil_0|url-access=registration|date=2000|publisher=Routledge|location=New York|isbn=0-415-92038-8|page=[https://archive.org/details/biographicaldict00ogil_0/page/654 654]}}<!--|access-date=23 October 2015--></ref> but must be used with caution as it does not provide necessary electrolytes and can cause [[hyponatremia]] or other [[electrolyte]] disturbances.
* Dextran also increases [[blood sugar]] levels.{{citation needed|date=December 2020}}
* Dextran can be used in an [[ATPS]] for [[PEGylation]]

===Laboratory uses===
* Dextran is used in the [[osmotic stress technique]] for applying [[osmotic pressure]] to biological molecules.
* It is also used in some size-exclusion [[chromatography]] matrices; an example is [[Sephadex]].
* Dextran has also been used in bead form to aid in [[bioreactor]] applications.
* Dextran has been used as an immobilization agent in [[biosensors]].
* Dextran preferentially binds to early [[endosomes]]; [[fluorescent]]-labelled dextran can be used to visualize these endosomes under a [[microscope]].
* Dextran can be used as a stabilizing coating to protect metal [[nanoparticles]] from [[oxidation]] and improve [[biocompatibility]].
* Dextran coupled with a fluorescent molecule such as [[fluorescein isothiocyanate]] 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]]<ref>Wang et al. [http://pubs.rsc.org/en/Content/ArticleLanding/2016/LC/C5LC01050K#!divAbstract "Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels"], [[Lab on a Chip (journal)]], 2016, 16, 282</ref>
* Dextran is used to make [[microcarriers]] for industrial cell culture
* Orally-administered [[dextran sodium sulphate]] is used to induce [[colitis]] in animal models of [[inflammatory bowel disease]].<ref>Murthy et al. [https://link.springer.com/article/10.1007/BF01303184 "Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin"], [[Digestive Diseases and Sciences]], 1993, 38, 1722</ref>
* Dextran is a common model compound to test the potential of drug formulations to facilitate intestinal absorption via the [[paracellular]] route.<ref>{{cite journal |last1=Guggi |first1=Davide |last2=Bernkop-Schnürch |first2=Andreas |title=Improved paracellular uptake by the combination of different types of permeation enhancers |journal=International Journal of Pharmaceutics |date=January 2005 |volume=288 |issue=1 |pages=141–150 |doi=10.1016/j.ijpharm.2004.09.023 |url=https://www.sciencedirect.com/science/article/pii/S037851730400571X}}</ref>

==Side effects==
Although relatively few side effects are associated with dextran use, these side effects can be very serious. These include [[anaphylaxis]],<ref>{{cite web|url=http://www.medicines.org.uk/emc/medicine/14139#UNDESIRABLE_EFFECTS|title=CosmoFer - Summary of Product Characteristics (SmPC) - (eMC)|website=www.medicines.org.uk}}</ref> volume overload, [[pulmonary edema]], [[cerebral edema]], or platelet dysfunction.

An uncommon but significant complication of dextran osmotic effect is [[acute kidney injury]].<ref>{{Cite journal|pmc=1689992|year=1976|last1=Feest|first1=TG|title=Low molecular weight dextran: A continuing cause of acute renal failure|volume=2|issue=6047|pages=1300|journal=British Medical Journal|doi=10.1136/bmj.2.6047.1300|pmid=1000202}}</ref> The pathogenesis of this kidney failure is the subject of many debates with direct toxic effect on tubules and [[Glomerulus (kidney)|glomerulus]] versus intraluminal hyperviscosity being some of the proposed mechanisms.{{citation needed|date=May 2013}} Patients with history of [[diabetes mellitus]], [[Kidney failure|chronic kidney disease]], or vascular disorders are most at risk.  Brooks and others recommend the avoidance of dextran therapy in patients with chronic kidney disease<!-- EXPLAIN and CrCl<40 cc per minute -->.

==Research==
Efforts have been made to develop modified dextran polymers.  One of these has [[acetal]] modified [[Hydroxy group|hydroxyl]] groups. It is [[Solubility|insoluble]] in water, but soluble in organic [[solvents]]. This allows it to be processed in the same manner as many [[polyesters]], like [[PLGA|poly(lactic-co-glycolic acid)]], through processes like solvent evaporation and [[emulsion]]. [[Acetalated dextran]] is structurally different from [[Acetyl group|acetylated]] dextran. As of 2017 several uses for [[drug delivery]] had been explored ''in vitro'' and a few had been tested in animal models.<ref name=Bachelder_review>{{cite journal |last1=Bachelder |first1=EM|last2=Pino|first2=EN|last3=Ainslie|first3=KM|title=Acetalated Dextran: A Tunable and Acid-Labile Biopolymer with Facile Synthesis and a Range of Applications|journal=Chem Rev|date=Feb 2017|volume=117|issue=3 |pages=1915–1926|pmid=28032507|doi=10.1021/acs.chemrev.6b00532}}</ref>

==See also==
* [[Dextran drug delivery systems]]
* [[Pentoxifylline]]

==References==
{{reflist|30em}}

==External links==
*[https://www.dextran.com/about-dextran/dextran-chemistry/dextran-structure Resource on dextran properties and structure of dextran polymers]
* {{MeshName|Dextrans}}

{{Carbohydrates}}
{{Blood substitutes and perfusion solutions}}
{{Authority control}}

[[Category:Biotechnology products]]
[[Category:Polysaccharides]]
[[Category:Intravenous fluids]]