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International Journal of Basic and Applied Sciences, 1 (3) (2012) 202-219
©Science Publishing Corporation
www.sciencepubco.com/index.php/IJBAS
An Insight To Pullulan: A Biopolymer in
Pharmaceutical Approaches
Deepak Kumar, Nisha Saini, Vinay Pandit, Sajid Ali*
School of Pharmaceutical Sciences, Shoolini University, Solan (H.P), India
Email: deepakkaushik354@gmail.com
School of Pharmaceutical Sciences, Shoolini University, Solan (H.P), India
Email: nishasaini10287@gmail.com
School of Pharmaceutical Sciences, Shoolini University, Solan (H.P), India
Email: vinay2121@gmail.com
School of Pharmaceutical Sciences, Shoolini University, Solan (H.P), India
Email: sajidalipharma4u@gmail.com*
Abstract
Pullulan is a non-ionic polysaccharide obtained from fermentation of
black yeast like Aureobasidium pullulans and is currently exploited in
food and pharmaceutical industries due to its unique characteristics.
Due to its properties like non-toxic, non-immunogenic, non-
carcinogenic, non-mutagenic, pullulan is being explored for various
biomedical applications viz., gene delivery, targeted drug therapy,
tissue engineering, wound healing, and also being used in diagnostic
applications like, perfusion, receptor, and lymph node target specific
imaging and vascular compartment imaging. The unique linkage of α
(1→4) and α (1→6) in pullulan endows this polymer with distinctive
physical traits, including adhesive property and the ability to form
fibres. This review article presents an overview of properties,
production, derivatives of pullulan, and recent advances of pullulan.
Keywords: Pullulan; Polysaccharide; Biomedical; Diagnostic application;
Medical imaging; Linkage.
1 Introduction
Biopolymers are the generally water soluble gums, produced by a variety of
micro-organism, which have novel and unique physical properties. Because of
these properties, these have found a wide range of applications in food,
pharmaceutical and other companies. Some of the applications include their use as
203
emulsifiers, stabilizers, binders, gelling agents, coagulants, lubricants, film
formers, thickening agents and suspending agents. Advances in technology occur
due to the exploitation of properties offered by new polymeric materials like
blends, composites, etc. Blend of polymers are prepared by physical mixing of
two or more polymers. The resulting blending system has the property superior to
any one of the individual polymer [1-3]. Pullulan is one of the polymers obtained
from the fermentation medium of the black yeast like Aureobasidium pullulans
(as it forms a black pigment, melanin so called black yeast) [4]. It shows activity
against for enzymes such as invertase, amylases, glucose oxidase, β-glusosidase,
frutosyltransferase, and small quantities of proteolytic enzyme [5-7]. Pullulan was
first reported by Bernier in 1958 and the structure was elaborated by Bender et al
in 1959 [8]. It comprises of maltotrose units connected by α (1→4) glycosidic
bond, whereas consecutive maltotriose units are connected to each other by α
(1→6) glycosidic linkages. Basic linkages in pullulan and its enzymatic
hydrolysis sites are shown in fig. 1.
Fig. 1: Basic linkages in pullulan and enzymatic hydrolysis site
Structure of pullulan and pullulan acetate are shown in fig. 2 and fig. 3
respectively. The application of pullulan is emerging as a source of polymeric
materials, which are economical and competitive with the natural gums produced
from marine algae and other plants [9]. Applications of pullulan biopolymer are
204
D. Kumar, N. Saini, V. Pandit, S. Ali
based on biodegradability of the polymer, so it is packed in food packaging films,
coating of food containers for perishable fruit and vegetables [10].
O
OH
OH
OH
O
O
OH
OH
CH2OH
O
O
OH
OH
CH2OH
O
HO
H2C
O
OH
OH
OH
O
O
O
O
O
CH2OH
OH
OH
OH
CH2OH
OH
Fig. 2: Structure of pullulan
O
OH
OH
OH
O
O
OH
OH
CH-OCOCH3
O
O
OH
OH
CH2OCOCH3
O
HO
H2C
O
OH
OH
OH
O
O
O
O
O
CH2OCOCH3
OH
OH
OH
CH2OCOCH3
OH
Fig. 3: Structure of pullulan acetate
2 Historical Aspects Related to Pullulan
Origin of pullulan occurred 6-7 decades earlier i.e. in 1950s. Aureobasidium
pullulans was first described as Dematium pullulans by De Bary. Bernier was the
first to isolate pullulan form Aureobasidium pullulans in 1958. Bender et al
studied the novel polysaccharides in 1959 and named it pullulan. In 1960s, the
basic structure of pullulan was resolved [11]. They discovered the enzyme
pullulanase, which hydrolyses α-(1→6) linkages in pullulan and converts to
maltotriose. Thus, pullulan is viewed as α-(1→6) linked polymer of maltotriose
205
subunits. Cately and his coworkers established the occurrence of randomly
distributed maltotetraose [12].
Pullulan has the safe history of use in Japan as a food ingredient and as
pharmaceutical bulking agent. The main use of pullulan has been as a glazing
agent having oxygen barrier properties [13]. It has Generally Regarded As Safe
(GRAS) status in US for a wide range of applications. Human volunteer studies
have only reported the abdominal fullness at doses of 10 g pullulan per day with
some mild gastrointestinal symptoms at higher doses. Pullulan is accepted for use
as an excipient in pharmaceutical tablets and is listed in the Japanese Standards
for Ingredients for drugs [14,15].
The commercial production of pullulan began in 1976 by the Hayashibra
Company, in Okayama Japan [16]. Pullulan production was an outgrowth of
starch syrup production, noted in 1883. Pullulan films were commercialized by
Hayashibara in 1982.
3 Properties of Pullulan
Dry pullulan is white to off-white tasteless, odourless powder which forms a
viscous non-hygroscopic solution when dissolved in water at 5-10%. Pullulan
starts to decompose at 250 ○C and chars at 280 ○C. it is highly soluble in water,
dilute alkali, insoluble in alcohol and other organic solvents expect
dimethylsulphoxide and formamide. As pullulan is highly water soluble so it can
be used as a carrier for drug and it helps in controlled release of drug in plasma. It
has the molecular weight within the range of 5000 – 9000000 g/mol with straight
unbranched chain and is very flexible molecule having the property of “random –
coil” (depending on sedimentation coefficient and intrinsic viscosity
measurement). Pullulan is non-toxic, non-mutagenic, non-carcinogenic, odorless,
tasteless, and edible [17,18]. Furthermore, pullulan has a considerable mechanical
strength and other functional properties viz. adhesiveness, film formability,
enzymatically – mediated degradability [19].
Pullulan is biodegradable, impermeable to oxygen, and is not attacked by the
digestive enzymes of the human gut, hence can be used as carrier for oral delivery
of drug. Pullulans solutions have relatively low viscosity, resembling gum arabic
[16]. It can be used as low-viscosity filler in berverages and sauces. The viscosity
of pullulan solution doesn’t change with heat, change in pH, and most metal ions
including sodium chloride.
4 Production of Pullulan
Pullulan is usually produced on industrial scale by the fermentation of liquefied
starch under specified parameters using a specific, not genetically modified, non-
pathogenic and non-toxigenic strain of Aureobasidium pullulans.
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D. Kumar, N. Saini, V. Pandit, S. Ali
4.1 Pullulan production by fermentation
The production of pullulan depends on the fermentation parameters viz., the
morphological state and the fungal strains. In commercial production [16],
Aureobasidium pullulans is cultivated on medium, comprises of starch
hydrolysates of dextran equivalent to 40-50, at 10-15% concentration. The
fermentation medium consists of peptone, phosphate and basal salts. The pH of
the culture media is initially adjusted to pH 6.5, which falls during the first 24
hours to a pH of 3.5. Maximal growth of culture media occurs within 75 hours.
Optimal pullulan yields are obtained within about 100 hours. Cultures are stirred,
aerated, and the temperature is maintained at temperature of 30 0C. Yield of
greater than 70% of initial substrate is claimed. Culture conditions and strain
selection are important parameters in obtaining high molecular weight pullulan,
which is relatively free of melanin. Aureobasidium pullulans cells are removed
from media by filtration of diluted culture broth. Melanin is removed by treating it
with activated charcoal. Pullulan is recovered and purified by precipitation with
organic solvents, particularly alcohol. It may be further purified by the use of
ultrafiltration and ion exchange resins.
Youssef et al reported the production of pullulan by using various strains of A.
pullulans using sucrose and glucose in shaking flask and stirred tank fermenters.
They reported maximum concentration of pullulan at 31.3 g/L with pullulan
productivity of 4.5 g/L per day [20]. In another study Shabtai and his co-workers
produced pullulan in a two stage fermentation process with increased productivity.
In the first step, fermentation was carried out using soyabean oil as a carbon
source and glutamate as nitrogen source, at pH of 4.5, which resulted in the
concentration of pullulan at 15 g/L. In the second stage, the cells were shifted to
production, which was carried out using sucrose as a carbon source with nitrogen
limitation. They reported the concentration of pullulan about 35 g/L in 50 hours
[21]. Recently, Roukas with his co-workers observed maximum concentration of
pullulan of 30 g/L in an air-lift fermentor at an aeration rate of 2 vvm
(vol/vol/min). West T. P., et al, 1991 produced the pullulan in two cycle process
of 165 hours, using either agar or calcium alginate for immobilized cell system.
The cells which were immobilized in alginate gave a higher production of
pullulan with 4.2 mg pullulan per gram cells per hour during the first cycle and
4.6 mg per gram cells per hour during the next cycle [22].
4.1.1 By using coconut by-products
Thirumavalavan et al synthesized pullulan from coconut by-products using
Aureobasidium pullulans. The strain was maintained on agar slants at 4 ○C and
subcultured every fortnight time interval. The seed medium comprises of sucrose,
potassium dihydrogen phosphate, yeast extract, ammonium sulphate, sodium
chloride and distilled water. The medium was autoclaved for 15 min at 121 ○C,
cooled and the pH was adjusted to 7. Then the culture was incubated at 30 ○C for
207
36 hours in a rotary shaker incubator at 200 rpm. The highest concentration of
pullulan was 54 g/L in coconut milk [23].
4.1.2 By beet molasses:
Goksungur and his co-workers produced pullulan by beet molasses using A.
pullulan. The media comprised of sucrose, ammonium sulphate, yeast, potassium
dihydrogen phosphate, magnesium sulphate, and sodium chloride. They reported
the highest pullulan concentration 35 g/L obtained in molasses treated with
sulphuric acid and activated carbon [24].
4.1.3 From agro-industrial waste:
Pullulan can be sysnthesized from a various carbohydrate substrates incorporated
into defined (synthetic) or non-defined media. The latter covers the agro-industrial
wastes, which have been shown to be suitable for pullulan production [25,26].
The utilization of these substrates for the production of pullulan seems to be
economically advantageous and economically sound.
Different fermentation parameters for the production of pullulan have been
studied with defined substrates viz. glucose and sucrose, but the results from the
agro-industrial wastes have shown that higher or similar yield of pullulan can be
obtained as compared to conventional substrate [27]. Also, pullulan produced by
such fermentations is characterized by heterogenecityof both composition and
molecular weight [28]. Following are the agro-industrial wastes which have been
used for the production of pullulans:
Grape skin pulp [28]
Molasses [28]
Starch waste [29]
Olive oil wastes [28,30]
Carob pod [22]
4.2 Biosynthesis of pullulan
Significant work has been done in recent years to determine the pathways for
biosynthesis of polysaccharides like pullulan. Taguchi et al noted the biosynthesis
of pullulan cell free preparations and acetone dried cells. Frozen cells were
disrupted by grinding by alumina. The debris was removed by centrifugation. The
precipitation of supernatant was done with 80% saturated ammonium sulphate
solution. This protein precipitate catalyzed biosynthesis of pullulan from Uridine-
5-diphosphoglucose (UDPG) and ATP gave the yield of 54% of pullulan with
respect to the amount of UDPG added [31].
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D. Kumar, N. Saini, V. Pandit, S. Ali
5 Semi Synthetic Derivatives of Pullulan
Pullulan can be easily derivatized in order to enhance its activity and widen the
window of its applications. Pullulan can be derivatized in various ways, which are
given below:
5.1 Chemical modification
Pullulan can be derivatized to enhance its applications by grafting different
chemical structures on the backbone. Pullulan consists of nine hydroxyl groups
for the substitution reactions on the repeating unit. The relativities of these
hydroxyl groups also depend on the polarity of the solvent and the reagents. The
hydroxyl groups of pullulan were subjected to various chemical reactions, leading
to the formation of a large number of derivatives, which are given in table 1 [32].
Table 1: Schematic chemical structures of the most common pullulan derivatives:
Type of reaction
Schematic chemical structure of substituted
pullulan (P-OH)
Etherification
Etherification
P-O-CH3 (Permethylation)
P-O-(CH2)2-3-CH3 (Alkylation)
P-O-CH2-COOH (Carboxymethylation)
P-O-(CH2)2-3-CH2-NH3+ (Cationization)
P-O-CH2-CH2-CN ( Cyanoethylation)
P-O-(CH2)1-4-Cl (Chloroalkylation)
P-O-CH2-CH2-(S=O)-CH3 (Sulfinylethylation)
P-O-CH2-CH2-CH2-SO3Na
P-O-CH2-CH2-N(CH2CH3)2
P-O-CH2-CH2-N+(CH2CH3)2-CH2-CH2-
N(CH2CH3)2
P-O-CO-CH3 (Acetylation)
P-O-CO-(CH2)2-14-CH3( Alkoylation)
P-O-CO-CH3-Cl (Chloroacetylation)
209
Esterification
P-O-CO-CH2-CH2-COOH (Succinoylation)
PA-O-CO-CH2-CH2-CO-Sulfodimethoxine a
P-O-CO-CH2-CH2-CO-Cholesterol b
P-abietate
P-strearate
PA-folate a
P-cinnamate
P-biotin
P-O-SO2-CH3
Urethane Derivatives
P-O-CO-NH-CH2-CH(OH)-CH3
P-O-CO-NH-CH2-CH2-NH3+
P-O-CO-NH-R (R=Phenyl or hexyl)
P-O-CO-NH-phenyl
Urethane
derivative\ amidification
P-O-CO-NH-(CH2)6-NH-CO-chloresterol
Chlorination
P-CH2-Cl (C6 Substitution)
Sulfation
P-O-SO3Na
Azido-pullulan
P-CH2-N2
Oxidation
P-COOH(C6 Oxidation)
Glycosidic ring opening ( periodate oxidation)
CMP/ hydrazone
derivativesc
P-O-CH2-CO-NH-doxorubicin
P-O-CH2-CO-NH-antibody
CMP/ amidificationc
P-O-CH2-CO-NH-CH2-(CH2)14-CH3
P-O-CH2-O-CO-C(CH3)2-R
with R= poly(methacrylate),
poly(methylmethacrylate)
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D. Kumar, N. Saini, V. Pandit, S. Ali
Copolymerization
poly(hydroxyethylmethacrylate) and
poly(sulfopropylmethacrylate)
P-O-CH2-O-CO-C(CH3)2-R
with R = poly (butylmethacrylate)
P-O-CH2-O-CO-C(CH3)2-R
with R= poly (N- isopropylacrylamide)
P-O-[CO-CH(CH3)-O]N-H (polylactide)
P-O-poly(2-isopropyl-2-oxazoline)
P - Pullulan
a Derivatives prepared from pullulan acetate (PA). Substitution occurred on
some of the remaining free hydroxyl groups
b Derivatives prepared from succinoylated pullulan. Substitution occurred on
carboxylic acid
c Derivatives prepared from carboxymethylpullulan (CMP). Substitution
occurred on carboxylic groups.
Chemical modification includes:
5.1.1 Carboxymethyl pullulan
Carboxymethylation is the most widely used reaction done on the neutral
polysaccharides in order to allow further chemical modification or to favor the
solubility in the aqueous solutions. The hydroxyl groups of the pullulan are
activated as alcoholate in the alkaline aqueous solution to allow the nucleophilic
substitution of chloride from monochloroacetic acid. Several works has been done
to understand the behavior of self assembled or cross-liked carboxymethyl
pullulan [33-36].
5.1.2 Sulphation
With the aim of developing a new alternative to heparin, pullulan was derivatized
by reacting with sulphur. The final property of sulphated pullulan depends on the
temperature, solvent and duration of action and the reagent used for the suphation.
Mahner et al reported a homogenous distribution of the sulphate along both
polysaccharidic backbones [37]. Later, Alban et al confirmed these results by
determining the degree of the sulphation of the hyrxyl group occurred in the order
C6 > C2 > C3 > C4 irrespective of the weight of the pullulan [38]. The sulphated
pullulans were obtained by stepwise sulphation of pullulans with SO3 – pyridinde
complex in dimethyl formamide (DMF) at 75 0C and 95 0C for 3 – 8 hours, in
which the pullulans having the molecular weight 50 kDa (soluble in DMF) and
200 kDa (insoluble in DMF) were used.
211
6 Applications of Pullulan
6.1 Biomedical and Pharmaceutical applications:
The use of pullulan in biomedical field is emerging contemporarily due to its
properties viz., non-toxic, non-immunogenic, biocompatible, and inert nature.
6.1.1 Tissue engineering and grafting
The surface and the bulk property of any biomaterial is important as it influences
the dynamic reactions that take place at tissue implant interface. These properties
or the change in the property which can take place over time in-vivo, should be
known for designing the biomaterial for specific applications and this can be
easily done with pullulan. Na and his co-workers conjugated the pullulan with an
interferon-water-soluble low molecular weight recombinant protein which had
both anti-viral and immunoregulatory activity. This allowed the user to preserve
the biological activity of the drug while enhancing its liver accumulation [39].
Surface modification is an utmost tool for tissue engineering purpose. The surface
modification can be easily done with pullulan as it comprises nine hydroxyl
groups for substation reactions on the repeating unit.
Applications of pullulan can be enhanced by grafting different chemical groups on
it as it contains nine hydroxyl groups, which can be easily substituted. The weight
of pullulan increases when grafting is done. The increase in weight of pullulan
after grafting clearly indicates the grafting of concerned group on to pullulan. Gao
et al characterized the graft yield, which is shown below [40]:
6.1.2 Pullulan as a carrier for drug delivery
Stimuli-sensitive polymer systems have been used as materials for the delivery of
drug [41,42]. Gheorge et al grafted poly(N-isopropylacrylamide-co-acrylamide)
onto the pullulan in order to confer their temperature sensitivity. Then the
remaining hydroxyl groups of the pullulan were reacted with succinic anhydride
Grafting ratio % G =
Weight of the grafted chain
Weight of pullulan
× 100
Grafting Efficiency % E =
Weight of the grafted chain
Weight of polymer formed
× 100
Grafting ratio % G =
Weight of the polymer used
Weight of the monomer used
× 100
212
D. Kumar, N. Saini, V. Pandit, S. Ali
to introduce the pH-sensitive units (-COOH), resulting into the more hydrophilic
nature than the native pullulan [43]. Thus, pH-sensitive pullulan microspheres can
be prepared for controlled delivery of the drug.
Liver targeting study focuses on the blood compatibility of the cationic
pullulan, physico-chemical characterization, uptake of nanocomplex by
hapatocytes and in-vitro transfection. Liver targeting can be achieved by
using drug loaded pullulan. Xi and his co-workers studied the liver binding
affinity of the modified pullulan in-vitro in hepatocytes and in-vivo in
mice [44].
Pullulan can be used for tumour cell targeting. Scomparin et al designed
two new anti-cancer polymers for tumour cell targeting. Pullulan was
derivatized with either doxorubicin or doxorubicin and folic acid. Then,
pullulan was activated by periodate oxidation and functionalized by
reductive conjugation cysteamine and 1.9 kDa ammonium
polyethyleneglycol [PEG (NH2)] [45]. This study suggests that
doxorubicin-pullulan bioconjugates possess suitable properties for passive
tumour targeting while folic acid conjugate of pullulan has a limited effect
on selective cell uptake.
6.1.3 Pullulan as a carrier for gene delivery:
Application of pullulan to the gene delivery is being explored. Gene therapy using
viruses have been performed, but the major drawback of using viruses is that they
are immunogenic, disease causing and can be hazardous to health. Pullulan being
non-toxic and biocompatible is investigated for gene delivery application.
Hosseinkhani et al mixed the pullulan derivative with a plasmid DNA in aqueous
solution containing zinc ions to obtain the conjugate of pullulan derivative with
plasmid DNA with Zn2+ coordination [46].
6.1.4 Medical imaging:
Recently nanotechnology has been used for earlier detection of cancerous cell in
the body. Quantum dots, which are the nano-size semiconductor particles has
attracted many scientists in biological field. They are used as fluorescent probes
for cell tracking. Hasegawa et al developed cholesterol pullulan and amino group
modified cholesterol pullulan nanaogels for the delivery of quantum dots into
cells in comparison to conventional cationic liposome which has the disadvantage
of forming aggregates ones gets into the cells. Nanoparticles were prepared by
mixing nanogels of derivatized pullulan with quantum dots. They reported the
intensity of fluorescence per cell and compared with liposomal-quantum dots
complex. The particles with higher number of amino group showed fluorescence
213
up to 3 – 4 times more than that of control. They concluded that cellular uptake of
cholesterol pullulan was enhanced by introducing cationic groups and
simultaneously the quantum dot’s better than the conventional cationic liposomes
and these nanoparticles could be a fluorescent probe for medical imaging [47].
6.2 Plasma expander
Pullulan was also explored as a potential blood-plasma substitute like that of
dextrans. Polymers which are highly water soluble in nature can be used as
plasma expanders and pullulan is water soluble polymer. It has been reported that
pullulan to be used as plasma expander with molecular weight of about 60 kDa
[16]. They observed that pullulan having high molecular weight increased the
venous pressure whereas low molecular weight pullulans were rapidly excluded
from the organism leaving the stage of secondary hemorrhagic shock. Thus,
pullulan to be used as plasma expander, should have an effective therapeutic range
of molecular weight. Shingel and his co-worker developed an anionically
modified pullulan via gamma irradiation which was used as a base for blood –
plasma substitute [48].
6.3 Molecular chaperons
Moleculaes having the chaperon like activity are able to catch and release proteins.
Molecular chaperons bind to denatured proteins in order to prevent irreversible
aggregation. Then chaperon molecules release the proteins. Water soluble
polymers such as polyethylene oxide (PEO) have been tried to increase the
recovery yield of parent protein during refolding [49]. These polymers prevent the
aggregation of proteins by blocking their hydrophobic surface. Nomura et al
developed hydrophobized pullulan nanogels having the properties of molecular
chaperons [50]. They reported the release of complexed proteins from the
nanogels in their refolded forms in the presence of cyclodextrins. They concluded
that these amphiphilic nanogels trap the denatured proteins and cyclodextrin acts
as an effector molecule to control the binding ability of chaperon molecule to
proteins.
6.4 Hydrophobized pullulan conjugates for drug delivery: A
recent development
Pullulan hydrogels as drug delivery systems in the form of microgels and
nanogels have been studied. Slow release of drug into the plasma helps in
attaining the therapeutic benefits [51]. Gupta and his co-worker prepared hydrogel
nanoparticles of cross-linked pullulans with glutaraldehyde in order to develop a
DNA carrier system, improving the gene loading efficacy, controlled release
214
D. Kumar, N. Saini, V. Pandit, S. Ali
properties, biocompatibility and enhanced stability. Also, hydrophobized pullulan-
based nanogels interact with molecular assemblies such as liposomes and oil-
water emulsion. As a result, hydrophobised pullulan conjugates were used for
targeting of drugs viz., metronidazole, nicotinic acid, sulfathilzole, mitoxantrone
and epirubicin [52].
Most of the cited paper in the field of hydrophobized pullulan reports the self
assembly of cholesterol-bearing pullulan as stable hydrogel nanoparticles in
which pullulan is non-covalently bind by associating cholesteryl moieties is
shown in fig. 4.
7 Recent Advances with Pullulan
Recent advances done in pullulan are described in table 2.
Pullulan
Cholesterol
Hydrophobic core
Hydrophilic
Outer shell
Self-assembly
Fig. 4: Formation of cholesterol-pullulan conjugate-based nanoparticles by self aggregation
in aqueous solution
215
Table 2: Recent advances of Pullulan:
Recent research
Advantages of pullulan
References
Fast disintegrating tablet
using pullulan as diluent
Tablet hardess was found to
increase without increasing the
disintegrating time with high
concentration of pullulan.
[53]
Pullulan /Silver
Nanoparticles composite
nanospheres using electrospray
techniques for antibacterial
application.
Controlled spherical structure by
controlling the concentration of
pullulan, enhanced antibacterial
activity
[54]
Self assembled nanogels of
hydrophobized pullulan
Size stability, micelles showed
long term colloidal stability with
nearly negative neutral charge
[55]
Pullulan acetate coated
magnetic nanoparticles for
hyperthermia
Nanoparticles have high magnetite
content, good biocompatibility, good
heating property in magnetic field,
and have evident cellular uptake by
tumor cells.
[56]
Rapid dissolving films of
cetirizine hydrochloride using
pullulan as a film forming agent
Pullulan acted as rapid film
forming agent.
[57]
8 Conclusion
Pullulan has gained a lot of attention in the past few decades due to its unique
properties. Pullulan is an edible and bio-polysaccharide with numerous
applications in the field of food and pharmaceutical industries. The unique
property of pullulan is due to its glycosidic linkage. Pullulan is synthesized by
fermentation of coconut by-products, beet molasses, agro-industrial waste.
Pullulan can be easily derivatized by means of chemical reaction. Pullulan has
important application in the field of biomedical and pharmaceutical field viz.,
tissue engineering & grafting. Pullulan has been used for liver and tumour target
delivery of drug. Pullulan has the application in the field of targeting of drug to
liver and cancer cells. Pullulan has occupied a niche area in food and
pharmaceutical field.
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