2. DEXTRAN ALSO KNOWN AS-Dextran sulfate sodium
sulfur18.
ACCORDINGTO USAN COUNCIL KNOWN AS –insulin I 131
Dextran 40,
interferon alfa-2a,etc
CAS NO.-9004-54-0
MOLAR MASS-VARIABLE.
COLOR-WHITE-OFFWHITE
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 (antiplatelet), 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 andStreptococcus
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.
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 DECREASESWITHTHE INCREASE INTHERMAL CONDITIONAND
BRANCHING.
DEXTRAN SULFATESARE SUPPLIED IN SODIUM SALT FORM MAKINGTHEM
STABEL &
SOLUBLE INWATER
DEAE-DEXTRANCAN BE STORED FOR 3YEAR.
IF IT IS UNOPENED IN EXTREMCONDITIONCAN BE KEPTAT 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
reducingerythrocyte aggregation and platelet adhesiveness. Dextrans also reduce factorVIII-
AgVonWillebrand 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. APPLICATIONS2)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 USEDTO 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 F1, 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