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Natural Polysaccharide for Nanotechnology Drug Delivery

Handrian Ramoko1, Dina Sofa Istifada1, Chairunnisa1, Paraswati1, Amelia Herlambang1

Faculty of Pharmacy, Padjadjaran University, Jatinangor, Indonesia


Nanotechnology drug delivery system has been developed for delivery of pharmaceutical active
agents into the target sites of the body. The pharmaceutical active agent could be delivered into
the target site by using natural polysaccharide. Polysaccharide has the potential as
nanotechnology drug delivery system with the high potential benefits of passive/active targeting
and reduced undesirable side effects. The mucoadhesive, biodegradable, and biocompatible
properties of polysaccharides can be used for increasing the efficiency of drug delivery system.
This study reviews recent advances made in using three common natural polysaccharide;
cellulose, alginate and chitosan in nanodrug delivery.

Introduction to individually designed carriers.

Nanoparticle carriers made of bioadhesive
Scientific research on
polysaccharides could prolong the residence
nanotechnology has received tremendous
time and therefore increase the absorbance
interest in this century due to its
of loaded drug5. Recent developments in
interdisciplinary applications in the field of
nanotechnology have shown that
catalysis, biomedicine, fuel cells, magnetic
nanoparticles (structures smaller than 100
data storage and energy technology41.
nm in at least one dimension) have a great
Nanotechnology increases bioavailability of
potential as drug carriers. Due to their small
drugs due to their specialized uptake
sizes, the nanostructures exhibit unique
mechanisms such as absorptive endocytosis
physicochemical and biological properties
and are able to remain in the blood
makes them a favorable material for
circulation for a longer time, releasing the
biomedical applications34. As drug delivery
incorporated drug in a controlled fashion
system, nanoparticles can entrap drugs or
leading to less plasma fluctuations and
biomolecules into their interior structures
minimizing side-effects9. Cell-specific
and absorb drugs or biomolecules onto their
targeting can be achieved by attaching drugs
exterior surfaces15. Nanotechnology
improves their performance and have abundant resources in nature and low
acceptability by increasing effectiveness, cost in their processing. Particularly, most of
safety, patient adherence, as well as natural polysaccharides have hydrophilic
ultimately reducing health care costs 9. The groups such as hydroxyl, carboxyl and
in vivo fate of nanoparticles developed as amino groups, which could form non-
drug delivery systems is influenced by the covalent bonds with biological tissues
surface characteristics of the colloidal forming bioadhesion11.
particles4.One of the ways to avoid the
According to structural
potential hazards of nanodrug delivery may
characteristics, nanoparticles are prepared
be by using natural polymers3. The results
mainly by four mechanisms, namely
showed that mobility depended on
covalent crosslinking, ionic crosslinking,
temperature, type, and molecular weight of
polyelectrolyte complexation, and self-
the polysaccharides4. Polysaccharides have a
assembly of hydrophobically modified
number of positive characteristics such
polysaccharides16. Polysaccharides have
biotolerability, biodegradability, protein
been especially used in the preparation of
rejecting ability, receptor interaction through
drug delivery systems32.
specific sugar moieties, and abundance of
functional groups for modification or This review therefore takes a look at the

functionalization21. recent advances made in using three

common natural polysaccharide; cellulose,
Polysaccharides are the polymers of
alginate and chitosan in nanodrug delivery.
monosaccharides. In nature, polysaccharides
have various resources from algal origin 1. Cellulose

(e.g. alginate), plant origin (e.g. pectin, guar Cellulose is the most abundant
gum), microbial origin (e.g. dextran, polysaccharide available worldwide and
xanthan gum), and animal origin (chitosan, exhibits attractive structure and single
chondroitin) . Due to the presence of properties, which are quite attractive for
various derivable groups on molecular both academic and industrial researchers21
chains, polysaccharides can be easily Cellulose based polymers has a positive
modified chemically and biochemically, characteristics such as safety,
resulting in many kinds of polysaccharide biodegradability, biocompatibility, and
derivatives. In addition, polysaccharides protein rejecting ability20. The hydrophilic
nature of the cellulose within paper structure USDA Forest Products Lab, Alberta
are very important for good fiber bonding26. Innovates-Technology Futures)18.
Chemical structure of the cellulose:
The current distribution of the
nanomaterials produced by type is
approximately 65% cellulose nanofibrils,
34% cellulose nanocrystals, and 1%
bacterial cellulose; however, this landscape
does not reflect the ease with which these
materials are produced and is likely to shift
due to the scale at which cellulose
nanocrystals can be produced and their
Cellulose represents ~ 1.5 x 1012 tons
numerous applications18.
of the total biomass produced yearly, and as
such is the most abundant structural polymer The amorphous nanoparticles (ANP)
in nature13. Cellulose has been used for are completely hydrolyzed by cellulolytic
millennia as a source of fuel, building enzymes with forming of glucose that can be
materials, paper products, and textile fibers. used further for biological, cosmetic or
Its widespread use is primarily due to the medical application. Low-acidic and soft
unique intrinsic physical, chemical, and nanoparticles can be used in cosmetic
mechanical properties that largely arise from formulation for gentle skin peeling. The
the hierarchical organization of natural ANP-TAS complexes can be applied in
cellulosic materials. For example, the tight remedies aimed for effective care and cure
packing of glucan chains contained in the of the skin10.
core of cellulose microfibrils gives plant cell
2. Alginate
walls the rigidity to withstand the
mechanical stresses of their environment18 Alginate, an anionic unbranched
biopolymer, is comprised of guluronic and
The appearance of the first pilot- and
mannuronic acid residues30. The most
industrial-scale producers of cellulose
common techniques used for the preparation
nanofibrils (e.g., Innventia, Borregard, Oji
of alginate nanoparticles are the reverse
Paper, VTT, Daicel) and cellulose
microemulsion, desolvation, cross-linking,
nanocrystals (e.g., CelluForce, Melodia,
and evaporation29. Alginate can interact with
the cationic components due to its anionic extensively applied as drug/gene delivery
nature. Therefore, it can be used for the systems23,37,43. The most common
preparation of delivery systems due to techniques used for the preparation of
incorporate positively charged drugs and alginate nanoparticles are the reverse
molecules. Calcium alginate is the most microemulsion43, evaporation38,
commonly used alginate matrix in the desolvation28, and cross-linking22. As a
engineering of drug/gene delivery systems37. polymeric acid alginate is negatively
charges in solution25.
Chemical structure of the alginate:
Alginate can interact with the
cationic components due to its anionic
nature. Therefore, it can be used for the
preparation of delivery systems due to
incorporate positively charged drugs and
molecules. Calcium alginate is the most
commonly used alginate matrix in the
34 engineering of drug/gene delivery systems37.

Alginate (ALG) is an air-soluble Alginate gel beads coated with

linear polysaccharide extracted from brown chitosan can prolong the residence time
sea weed and is composed of alternating through the storage and in vivo circulation.
blocks of α-L-guluronic and β-dmannuronic Besides, alginate-chitosan complex was
acid residues. ALG has been known to shown as a promising system for the
possess mucoadhesive, biodegradable, and controlled release of incorporated agents
biocompatible properties and has potential compared to either alginate or chitosan
for various pharmaceutical and biomedical alone7. Alginate nanoparticles have also
applications such as drug delivery systems been developed to promote the
and cell encapsulation12. bioavailability of antitubercular drugs
(isoniazid, pyrazinamide, ethambutol, and
Alginate nanoparticles owing to
biocompatibility, biodegradability,
nonantigenicity, gelation ability, and Alginate can serve as an effective
mucoadhesive advantages have been natural disintegrant, as a tablet binder and
offer an attractive alternative to a sustainable is a natural biopolymer that derived from
release system8. Alginates offer advantages partial hydrolysis of collagen. Cell
over synthetic polymers because they can attachment to chitosan is mainly attributed
form hydrogels below the pH and relatively to electrostatic interactions between the
lightweight temperatures and can be chitosan cationic sites, and the negatively
considered non-toxic, biocompatible, charged carboxylate and sulphate groups
biodegradable, in terms of cheaper and found in cell-surface36. Recently, water-
abundant alginate prices available in nature; soluble chitosan derivatives were also be
In addition, alginates meet the essential ionically cross-linked to prepare
requirements for receiving sterilization and nanoparticles42.
storage. It can be seen from this advantage
Chemical structure of the chitosan:
that makes alginate a very useful material
for biomedical applications, especially for
the delivery of controlled drugs and other
biologically active compounds and for cell
encapsulation. Calcium alginate is a natural
haemostat, so an alginate-based dressing is
indicated for bleeding wounds35.

Sodium alginate may be used as a 33

binder and disintegration of the tablets, as
Chitosan composed of D-
suspending agents and thickeners in gel,
glucosamine repeating units, is known as a
lotion, and air-soluble creams, and as
non-toxic, biodegradable, bioadhesive
stabilizers for emulsions. Traditionally,
polysaccharide and is structurally similar to
sodium alginate has been used as a tablet-
the cellulose except that amine groups give
binding agent, while alginic acid as a
chitosan its net positive charge29.
disintegrant tablet in compressed tablets is
designed for immediate drug release39. Chitosan is a biodegradable polymer
obtained from chitin deacetylation, which is
3. Chitosan
contained in insect shells and marine
Chitosan is a natural polysaccharide crustaceans. chitosan is a marine based
derived from waste Crustaceae and gelatine polymer27.
Chitosan has unique properties, mucoadhesive, biodegradable, and
among others, biodegradability, bioactivity, biocompatible properties of the
non-toxicity and good adhesion in polysaccharide could be used as
absorption17. As a polumeric amine, pharmaceutical and biomedical applications
chitosan is positively charges when such as drug delivery systems. However, the
dissolved in weak aqueous acidic solution25 interaction and mechanism between the
pharmaceutical drugs and polysaccharide as
Chitosan exhibits superior
nanotechnology drug delivery in vivo at
mucoadhesive properties and is able to open
molecular level should be studied further.
tight junctions between the epithelial cells
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