Декстран: құрамы, қасиеттері және медицинадағы қолданысы

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". Dextran chains are of varying lengths (from 3 to 2000 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.

Dextran was discovered by Louis Pasteur as a microbial product in wine, but mass production was only possible after the development by Allene Jeanes of a process using bacteria. Dextran is a complicating contaminant in the refining of sugar because it elevates the viscosity of sucrose solutions and fouls plumbing. 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 fructans, which can complicate isolation of the dextrans. Medicinally it is used as an antithrombotic (antiplatelet), to reduce blood viscosity, and as a volume expander in hypovolaemia.

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). 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 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 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.

Although relatively few side effects are associated with dextran use, these side effects can be very serious. These include anaphylaxis, volume overload, pulmonary edema, cerebral edema, or platelet dysfunction. An uncommon but significant complication of dextran osmotic effect is acute kidney injury. The pathogenesis of this kidney failure is the subject of many debates with direct toxic effect on tubules and glomerulus versus intraluminal hyperviscosity being some of the proposed mechanisms. Patients with history of diabetes mellitus, 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.

Efforts have been made to develop modified dextran polymers. One of these has acetal modified hydroxyl groups. It is insoluble in water, but soluble in organic solvents. 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. Acetalated dextran 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.