Dextran presentation

it include properties detail,bioavalability,compatibility,application.

1. SUBMITTED BY-PRIYANKA JHA TOPIC-DEXTRAN POLYMER. SUB-M.PHARMA(PHARMACEUTICS ) DEXTRAN POLYMER

2. DEXTRAN ALSO KNOWN AS-Dextran sulfate sodium sulfur18. ACCORDING TO USAN COUNCIL KNOWN AS –insulin I 131 Dextran 40, interferon alfa-2a,etc CAS NO.-9004-54-0 MOLAR MASS-VARIABLE. COLOR- WHITE-OFFWHITE Dextran polymer

3. Chemical name DEXTRAN ,ALPHA-D-GLUCOSYL-1-6-ALPHA-D-GLUCOSE,AC1N49C8 MOLECULAR FORMULA C 18 H 32 O 16 MOLECULAR WEIGHT 504.43708G/MOL USED Anticoagulant,plasma volume expander Chemical formula H(C 6 H 10 O 5)OH

4. Dextran  is a complex branched  glucan  ( polysaccharide  made of many  glucose  molecules) composed of chains of varying lengths (from 3 to 2000  kilodaltons ). It is used medicinally as an  antithrombotic  (anti platelet ), to reduce blood  viscosity , and as a volume expander in  hypovolaemia . The straight chain consists of α-1,6  glycosidic  linkages between glucose molecules, while branches begin from α-1,3 linkages. Dextran is synthesized from sucrose by certain lactic acid bacteria, the best-known being  Leuconostoc mesenteroides  and Streptococcus mutans .  Dental plaque  is rich in dextrans. Dextran was first discovered by  Louis Pasteur  as a microbial product in wine.Dextran 70 is on the  WHO Model List of Essential Medicines , the most important medications needed in a basic  health system . TEMPRATURE-25*C (77*F),100kpa.

5. TYPES OF DEXTRAN DEXTRAN 110 DEXTRAN 70 D-40 D-70 D-111

6. Dextran Properties Dextran Characteristics: Dextran fractions are characterized by their average molecular weights and molecular weight distributions. Dextran is used in various fields such as pharmaceutical, photographic, and agricultural industries. The versatile use of Dextran products relates to the favorable properties: Dextran is neutral and water soluble. Dextran is easily filtered. Dextran is biocompatible. Dextran is biodegradable. Dextran is stable for more than 5 years.

7. Dextran Structure Dextran is an α-D-1,6-glucose-linked glucan with side-chains 1-3 linked to the backbone units of the Dextran biopolymer. The degree of branching is approximately 5%. The branches are mostly 1-2 glucose units long. Dextran can be obtained from fermentation of sucrose-containing media by  Leuconostoc mesenteroides B512F. A fragment of the Dextran structure is illustrated in Figure 1. Fig. 1:   Dextran is a glucose polymer in which the linkages are predominantly of the α(1,6) type. The degree of α(1,3) branching is generally less than 5% and decreases with decreasing molecular weight

8. Biocompatibility The clinical use of Dextrans over the past 50 years provides impressive proof of their safety and quality. Most of the safety studies have been related to parenterally administered Dextran solutions in the molecular weight range 40,000 (Dextran 40) to 70,000 (Dextran 70). The intravenous mean lethal dose of Dextran 70 fraction is 55 g/kg bodyweight in mice, 18 g/kg bodyweight in rabbits, and 10 g/kg bodyweight in dogs. Dextran may be ingested orally and is well tolerated. The ingestion of Dextran is followed by a rapid increase in blood sugar and liver glycogen and is thus digestible. Dextran is an ingredient of solutions for ophthalmic use, for intrauterine examinations, and is also used in creams and ointments . It may therefore be concluded that Dextran has an excellent record of biocompatibility. Pharmacosmos is a manufacturer of Pharmaceutical Quality Dextran including  Dextran 1 ,  Dextran 40 ,  Dextran 60 , and  Dextran 70   according to pharmacopoeial specifications, for example EP, USP, and JP. Many other applications of Dextran in medicine have appeared

9. Biogradeabillity of Dextran Enzymes (dextranases) from molds such as Penicillium  and Verticillium have been shown to degrade Dextran: (1 ). The products are essentially low molecular weight sugars, for example glucose, isomaltose etc. Similarly many bacteria produce extracellular dextranases that split Dextran into low molecular weight sugars ( 2). Examples of these are Lactobacillus,  Cellvibrio , Cytophaga, and soil Bacillus spp . Dextran is therefore biodegradable and the Dextran by-products are readily absorbed into the natural environment.

10. Physical-chemical properties SOLUBILITY- Dextran B-512(F) is freely soluble in water, methyl sulphoxide, formamide, ethylene glycol, glycerol 4-methylmorpholine-4-oxide , and hexamethylphosphoramide (a carcinogenic). Some dextran fractions may adopt a certain degree of crystallinity and may only be brought into solution by strong heating . The molecular weight of native dextran NRRL B-512(F) has been investigated in many laboratories (46-51 ) and values for the MW from 9 x 106 to 500 x 106 have been obtained. Measurements in avariety of solvents, for example 4 M NaCl and 6 M urea, failed to reveal any evidence that association contributed to these exceedingly high values (49, 50). The relationship between MW and intrinsic viscosity [h] has been investigated over a wide range of MW.

11. STABILITY- STABILITY DECREASES WITH THE INCREASE IN THERMAL CONDITION AND BRANCHING. DEXTRAN SULFATES ARE SUPPLIED IN SODIUM SALT FORM MAKING THEM STABEL & SOLUBLE IN WATER DEAE-DEXTRAN CAN BE STORED FOR 3 YEAR. IF IT IS UNOPENED IN EXTREM CONDITION CAN BE KEPT AT 4*C FOR 6 MONTHS. Dry Substance Dextran Powder Dextran fractions are stable for more than 5 years when stored as a dry substance Dextran powder in well-sealed containers at room temperature. Dextran powder will slowly absorb moisture when exposed to air or when stored in non-air tight containers. Dextran Solutions and Sterilization Dextran solutions may be sterilized by heating in an autoclave. These solutions are stable for many years and are best stored at constant temperature. pH -The optimal pH for storage is between 6–7. However, Dextran is stable at ambient temperatures for extended periods in the pH range 4–10. Other techniques for sterilization of Dextran solutions, for example irradiation, may lead to degradation. During autoclaving a slight decrease in pH and a slight yellowing may be observed, which does not affect Dextran fraction solutions or performance. The sterilization of Dextran solutions does not affect the molecular weight distribution of the Dextran .

12. 1)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 . By inhibiting α-2 antiplasmin, dextran serves as a  plasminogen  activator, so possesses  thrombolytic  features. Outside from 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 3,000 Da to 2,000,000 Da. 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. APPLICATION

13. APPLICATIONS 2)Other medical uses It is used in some  eye drops  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 .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, but must be used with caution as it does not provide necessary electrolytes and can cause  hyponatremia  or other  electrolyte  disturbances. It also increases  blood sugar  levels. 3)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 in immobilization in biosensors. Dextran preferentially binds to early  endosomes ; fluorescent-labelled dextran can be used to visualize these endosomes under a fluorescent 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.

14. Labeled dextrans are hydrophilic polysaccharides most commonly used in microscopic studies to monitor cell division, track the movement of live cells, and to report the hydrodynamic properties of the cytoplasmic matrix. The labeled dextran is commonly introduced into the cells via microinjection. Key Applications Using Labeled Dextrans There are a multitude of citations describing the use of labeled dextrans. Some of the most common uses include: •  Neuronal tracing (anterograde and retrograde) in live cells •  Cell lineage tracing in live cells •  Neuroanatomical tracing •  Examining intercellular communications (e.g., in gap junctions, during wound healing, and during embryonic development) •  Investigating vascular permeability and blood–brain barrier integrity •  Tracking endocytosis •  Monitoring acidification (some dextran–dye conjugates are pH-sensitive) •  Studying the hydrodynamic properties of the cytoplasmic matrix 4)APPLICATION OF DEXTRAN-LABELED DEXTRAN:-

15. 5- APPLICATION IN LYOPHLISATION: DEXTRAN used in various lyophilized formulations of small molecules. The role of excipients such as bulking agents, buffering agents, tonicity modifiers, antimicrobial agents, surfactants and co-solvents has been discussed. Additionally, a decision making process for their incorporation into the formulation matrix has been proposed. A list of ingredients used in lyophilized formulations marketed in USA has been created based on a survey of the Physician Desk. { Reference ( PDR) and the Handbook on Injectable Drugs. Information on the recommended quantities of various excipients has also been provided, based on the details given in the Inactive Ingredient Guide (IIG)} EG: Amphotec(DEXTRAN USED TO PREPARE SMALL MOLECULE ) Caverject , Rubex, Sodium edecrin, Fludara, Cytovene.

16. 6).Use of dextran nanoparticle: A paradigm shift in bacterial exopolysaccharide based biomedical applications: This review is a concise compilation of all the major researches on dextran nanoparticle based biomedical applications. Dextran is a highly biocompatible and biodegradable neutral bacterial exopolysaccharide with simple repeating glucose subunits. It’s simple yet unique biopolymeric nature made it highly suitable as nanomedicine, nanodrug carrier, and cell imaging system or nanobiosensor. Most importantly, it is extremely water soluble and shows no post drug delivery cellular toxicity. Complete metabolism of dextran is possible inside body thus possibility of renal failure is minimum. Dextran based nanoparticles have superior aqueous solubility, high cargo capacity and intrinsic viscosity, and short storage period. The main focus area of this review is- past and present of major biomedical applications of dextran based nanomaterials thus showing a paradigm shift in bacterial exopolysaccharide based nanobiotechnology. 7)application Dextran is used to make  microcarriers  for industrial cell culture.

17. 8 .Application research on dextran-based hydrogel and its drug controlled release [Article in Chinese] Chen F 1 ,  Wu Z ,  Jin Y . Abstract OBJECTIVE: To introduce the development of dextran-based hydrogel and its drug delivery system in drug sustained and/or controlled release, and to investigate their application in tissue engineering. METHODS: Related literature was extensively reviewed and comprehensively analyzed. RESULTS: In recent years, great progress was made in the studies of dextran-based hydrogels and study on dextran-based intelligent materials became an investigative hotspot especially in tissue engineering. CONCLUSION: Dextran-based hydrogel is considered to be a good potential material in field of drug delivery and tissue engineering. Endowed with new characteristics, a series of intelligent biomaterials can be derived from dextran-based hydrogels,which can be widely used in biomedicine. Further study should be done on the industrialization of its interrelated production.

18. Although relatively few side effects are associated with dextran use, these side effects can be very serious. These include  1)anaphylaxis , 2)volume overload, 3)  pulmonary edema , cerebral edema , or platelet dysfunction. 4)An uncommon but significant complication of dextran osmotic effect is  acute renal failure . The pathogenesis of this renal 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 ,  renal insufficiency , or vascular disorders are most at risk. Brooks and others recommend the avoidance of dextran therapy in patients with  chronic renal insufficiency . SIDE EFFECTS

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