Mini review of polysaccharide nanoparticles and drug delivery process

1. Advances in Applied NanoBio-Technologies 2020, Volume 1, Issue 2, Pages: 33-44
33
Mini review of polysaccharide nanoparticles and
drug delivery process
Farzad Raeisi a*, Elham Raeisi a
a
Department of Chemical Engineering, University of Mohaghegh Ardabili (UMA), Ardabil, Iran.
Received: 24/04/2020 Accepted: 01/06/2020 Published: 20/06/2020
Abstract
In recent years, according to research, the role of polysaccharides as drug carriers has attracted much attention. Polysaccharide
nanoparticles have been considered as vesicles of various pharmaceutical agents due to the existence of special multifunctional
groups in addition to physicochemical properties such as biocompatibility and biodegradation. The presence of groups with
different applications on the main constituent structure of the polysaccharide allows easy chemical or biochemical modification for
the synthesis of polysaccharide-based nanoparticles with different structures. Nanogels with polysaccharide base and structure have
high water content, large surface area for polyvalent biological binding, adjustable size and internal network for combining different
drugs. These special properties make it possible to use polysaccharide-based nanogels in drug delivery systems.
Keywords: Polysaccharide, Nanoparticles, Drug delivery
1 Introduction
What can be understood by researchers is the solubility,
permeability and metabolic stability of a drug molecule is one of
the main applications in drug delivery systems [1,2]. Drug
delivery systems (DDS) are based on interdisciplinary
information and knowledge that combines polymer science, bio-
bonding chemistry, pharmacy and biomolecular [3]. The main
purpose of DDS is to transfer drug agents to systemic circulation
based on pharmacokinetic control, pharmacodynamics, non-
immunogenicity, non-specific toxicity and bio-identification of
the target site to create the desired drug effect [4,5]. Important and
effective cases of DDS compared to the old methods, the tendency
to provide the drug selectively and specifically to a specific
situation, eliminating the amount of too much or less (keeping the
level of the drug in the desired range), increasing the body's
acceptance rate After using the drug, the patient is more effective
absorption of the drug in the desired cell and prevention of side
effects [6]. Nanoparticles (NPs) with a diameter of 10 to 1000 nm
have special effects (such as: their surface area is high, their
quantum properties and the ability to absorb and carry other
compounds) that make them an important method and tool in drug
delivery systems. Converts [7-9]. Therefore, their relatively high
(effective) levels, NPs, can block or immobilize large volumes of
anticancer drugs through covalent interactions [10,11]. According
Corresponding author: F.Raeisi, Department of Chemical
Engineering, University of Mohaghegh Ardabili, Ardabil, Iran.
E-mail: Raeisi.farzad@yahoo.com
to these findings, NPs composed of biocompatible and
biodegradable polymers can be used in DDS [12]. Polymeric
nanocarriers of natural proteins (such as albumin, collagen,
gelatin, etc.) [13-15] or synthetic polymers (such as
polyacrylamide (PAA), polylactic acid (PLA), polyglycolic acid
(PGA)), Poly (lactide-co-glycolide) (PLGA), dendrimers, etc. are
probably formed [16-21]. Nowadays, polysaccharide-based
nanoparticles due to the existence of special multifunctional
groups, in addition to physicochemical properties, including
biocompatibility and biodegradation, have been considered as
vesicles of various pharmaceutical agents [22,23].
One of the advantages of polysaccharides is that they maintain
several recognition functions, allow the identification or adhesion
of a specific receptor, as well as provide a neutral coating with
low surface energy and prevent the uptake of non-specific
proteins [24]. Also, the presence of multifunctional groups (such
as hydroxyl, carboxyl, and amine groups) on the main
polysaccharide form allows a chemical or enzymatic combination
with several molecules. Abundance in nature, biocompatibility,
biodegradation, low immunogenicity, and simple chemical or
enzymatic modification make polysaccharides the best choice for
the synthesis of NPs in DDS [25]. The most important drawback
of using polysaccharides for drug delivery can be their natural
diversity and difficult laboratory synthesis.
2 Polysaccharides
Polysaccharides are a group of carbohydrates with a large
polymeric oligosaccharide formed through glycosidic bonds in
the presence of multiple monosaccharides [26]. In nature, the
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main source of polysaccharides (e.g. pectin, cellulose, starch), in
animals (chitosan, chitin, glycosaminoglycan), in the microbial
domain (e.g. dextran, pololan, xanthan gum, gelan gum) and algal
origin (to Examples are agar, alginate and carrageenan) [27,28].
Depending on the composition of the monosaccharide units, the
polysaccharide can be classified as homopolymers (e.g. it consists
of monosaccharide repeats such as glycogen, starch, cellulose,
pololan, pectin) or heteropolymers (e.g. composed of different
monosaccharide units, e.g. Chitosan, heparin, hyaluronic acid,
chondroitin sulfate, creatine sulfate, heparan sulfate and dermatan
sulfate) [29-31]. Due to the abundance of polysaccharides in
nature, lower analysis costs, biocompatibility, biodegradability,
non-toxicity, water solubility and viability are one of the most
suitable biomaterials in nanomedicine. [32-34] In addition,
polysaccharides have a large number of reactive functional
groups (such as hydroxyl, amino, and carboxylic acids) in their
core structure, which facilitate the extraction process and
contribute to their structural and reaction diversity [35]. And
because of the biodegradation and non-toxic end products that are
obtained, there are currently many studies have been and
researches on polysaccharides and their families for their special
use as nanoparticles (such as nanogels or micelles) in drug
delivery systems.
Figure 1: Hyaluronic acid and Heparin Structure [149].
2.1 Hyaloronic acid
On of natural mucopolysaccharides is hyaluronic acid (HA)
and has many beneficial benefits including compatibility, lake of
immunogenicity, chemical adaptability, non-toxicity,
degradability and high hydrophobicity [36]. HA is found in much
concentrations in different soft crossbred tissues such as synovial
fluid, vitreous shock, skin and umbilical cord [37]. Hyaluronic
acid, which is made of repetition of N-acetyl-d glucosamine and
D glucuronide diacaridic units, is isolated from the synapse
junction and mammalian connective tissue and is a natural
degradable polymer [38]. The molecular weight of the HA
molecule was define with the number of repetitive units, which
can vary from 1x105 Da to 2x106, also cellular interaction [39].
The short string of HA components, usually in the range of 200
kDa, show a response in inflammatory macrophages, creating
explanation in a number of inflammatory mediators [40]. Tall HA
strings play an important role in ECM structure and mechanical
properties [41,42]. One of the main parts in the extracellular
matrix of cell membrane chondrocytes (ECM), as a structural
element HA hyaluronic acid had a linear polysaccharide structure
that acted, preparing support for the distribution of components
[43-45]. Among the components of ECM (collagen, elastin,
fibronectin, elastic fibers) [46], hyaluronic acid (HA) is the main
feature of fibrotic processes. HA is a non-sulfate glycosamine
aminoglycan that is synthesized by three HA transmembrane
synthesizers (HAS1, HAS2, and HAS3) and binds specific
protein components [47]. HA is the essential ingredient in
epidermis and dermis in the skin and is a great moisturizer [48].
Interacting with endothelial cell receptors (CD44) studies have
shown that HA to increase cell reproduction and raise
angiogenesis, increase collagen deposition, and develop re-
epithelialize skin regeneration [38]. It was also known for
regulating signal transmission, cell migration, and different
oregntations [45,49,50]. In addition, HA changes rapidly in the
body with hyaluronidase, and their half-life varies from hours to
days [38]. Furthermore to CD44, in cancer cells there are several
so many-expressed HA-binding receptors in comparison to
normal cells, like endocytic lymphatic receptor (LYVE-1)
receptor [51], and receptor for mediated hyaluronic acid
(RHAMM) [52]. These receptors can target the tumor selectively.
The duty of CD44 in the interaction among HA and particular
cells has been extensively investigated. The CD44 family of
proteins belongs to transmembrane glycoproteins and membrane
processes and plays a main duty in extracellular adhesion, cellular
activity, and signal transmission [53]. In tumor attack and
metastasis in cancer cells the CD44 receptor is important and is
related with cellular adhesion, including association and
migration in natural biological systems [54,55]. RHAMM is
another famous HA receptor that mediates cell multiplication and
migration and is weak in most normal tissues. In contrast,
RHAMM shows a growth in expression in tumor cells that is
related to metastases. First advantage of HA is that HA increase
the anticancer drugs resistance in physiological conditions [56].
Second, HA can solve forms of current anticancer drugs, like low-
specificity, through several obvious receptors that are selectively
attached to HA [57,58]. Finally, HA can be chemically modified
through functional groups. Carboxyl groups in the glucuronic acid
unit and hydroxyl groups primarily in the N- acetyl -D-
glucosamine unit are typically used chemically modifed to obtain
HA formative [36,59,60] For more than three decades HA and its
formatives have been clinically used as medical products. Now a
day, in tissue engineering and regenerative medicine HA has been

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known as a main building block for new biological materials [61].
For used in three-dimensional biodegradability, HA has been
chemically modified into gels, which are usually made by
disulfide, in addition to hydrazide, enzymes, and clicks. Among
these changes, the thiol modified HA (HA-SH) automatically, but
slowly, to form a hydrogel crosses in the air. To produce a porous
sponge the gel can be dried to make a thin film or lyophilized [38].
For progress the mechanical stability of hydrogels, nanoparticle
compounds, double-mesh or double-walled tactics were used
[62]. Bilateral hydrogels are often powerful than hydrogels with
detached components and have higher chemical constant and
adjustable swelling attributes [38,63-65]. Because HA can absorb
water, it is catching remarkable consideration from researchers
for medical usages including drug delivery systems, by producing
viscoelastic gel, [36,66,67]. Hyaluronic acid (HA) is a natural
polysaccharide with nice biocompatibility and decompositibility.
HA and its derivatives can be used as carriers of permanent drug
release, which can delay drug release and have a long-time affect.
They can be used to transfer several drugs such as proteins,
nucleic acids and anti-tumor drugs. HA and its formatives in
particular can attach to several receptors on the cell surface and
can be used for aimed drug transfer, particularly for the transfer
of antitumor drugs.so, there are several forms of tumor aimed
drug transfer systems based on HA [68]. Hyaluronic acid has nice
biocompatibility, biodegradability and nonimmunogenicity.
Furthermore, it has the ability to detect specific receptors that are
overexpressed on the surface of tumor cells, and cancer drugs can
be targeted at tumor cells to kill them better. Therefore,
hyaluronic acid has been highly regarded as a means of
transporting drugs [69]. HA and its formatives can be used as
vectors in different drug transfer systems. Based on various forms
of vectors, they can be divided into nanoparticle drug transfer
system [70-72], gel drug transfer system [73], cationic transfer
system of polymer as gene drug vector [74], nanoemulsion
transfer system [75], polyelectrolyte microcapsule transfer system
[76], microsphere drug transfer system [77], film agent transfer
system [78], etc. Here, research improvement in different forms
of drug transfer systems aimed at tumor-based The basis of HA
was highlighted, including the transfer system of tumor-targeted
drug for drug conjugate, the transfer system of tumor-targeted
drug with amphiphilic formative HA, the targeted drug delivery
of modified system-level tumor, and the target drug of tumor for
gene drug with HA [68]. In last years, HA and its formatives have
been used as a means of transportation for steroid drugs,
polypeptides and protein drugs, also different anticancer drugs
[79]. This new type of drug vector can significantly extend the
shelf life of the drug at the site of management decrease the
number of management, growth bioavailability, and decrease
harmful responses [80]. In drug delivery to cells, HA and
polycation compounds majorly get better serum stability and can
detect and bind to specific receptors expressed on cancer cell
membranes through receptor-mediated endocytosis [81].
Targeting intracellular transmission of nucleic acids and other
drugs has high potential for clinical use [68,82]. The targeted drug
transmission system is based on HA drug compounds and prodrug
drug compounds produced by covalent bonding of small molecule
anti-tumor drugs to HA. These covalent bonds do not crack easily
in the blood, but after reaching the target, they are broken down
by hydrolysis or enzymolysis and release the drug. HA drug
compounds can increase drug solubility, change drug distribution
and half-life in the body, raise tumor tissue accumulation by
increasing the effect of osmotic retention, and improve drug effect
[68,83]. Major issues with self-piced up nanoparticles for drug
vectors for cancer tratment include viability and tumor
targetability because immature drug escap and nonspecific
accumulation of drug-loaded nanoparticles may cause harmful
toxicity to normal members and therapeutic efficacy be less [84].
HA increases liposome resistance and increases skin penetrance
and the ability to target drugs in pharmacological drugs (e.g.
hydrophobic cyclosporine) [37]. For increase aggregation at
tumor sites while reducing unwanted toxicity, one possible
solution to this challenge is that two separate tumor-specific
ligands may be involved in localization [85]. In order to prolong
the release time of protein drugs, HA hydrogels have been widely
studied a new storage system for encapsulation of protein drugs
[68,86]. Hyaluronic acid, with its biodegradability as a polymer,
has been used extensively in the drug delivery process. Although
most tests are laboratory, the results of in vivo tests are very
specific. These results make it possible that with the discovery of
new drugs and the development of new methods, the percentage
of hyaluronic acid obtained as a drug will be even higher. Despite
the widespread use of drug delivery methods, there is still little
focus on hyaluronic acid. In addition, despite the development
and use of drug delivery agents and diversity, targeting chemical
modification of hyaluronic acid is still limited. Therefore,
research in the field of hyaluronic acid derivatives should be
strengthened to continuously optimize drug delivery. There has
been a lot of scientific research on hyaluronic acid as a carrier of
various drugs, but most of them are in the laboratory research
phase [69]. Bio-in vivo distribution showed that HA nanogels
increased DOX accumulation at the tumor area compared to free
DOX and longer DOX circulation time [37]. It has been suggested
that amphotericin B be transferred to the vaginal mucosa for
vulvovaginal candidiasis [87,88]. Cholesterol is generally used as
a hydrophobic component for the compound of nanogels through
self-assembly of amphiphilic copolymers based on hydrophilic /
hydrophobic equilibrium [89]. He et al. [90] Cholesterol-
hyaluronic acid (CHA) nanogel compounds for the effective
treatment of cancer cells, especially drug-resistant and expressive
cancer cells [37] HA-based drug transfer vectors can provide
solubility and solvability to anti-cancer drugs in biological
environments and provide targeted cancer treatments. Based on
these advantages, HA has been studied as a promising substance
in the extension of progressive clinical cancer therapies in several
formulations including nanoparticles, micelles, liposomes and
hydrogels, among others [36]. Recently from bronchoalveolar

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lavage (BAL) in CTD-ILD or BOS affected patients we have
shown that primary lung fibroblasts (LF) isolated express a high
level of HA CD44 receptor, and this receptor represents a suitable
and beneficial molecule that Its use can target nanoparticles. [91].
Nano-carriers with HA function are preferred in the treatment of
cancer [92-95], but given the important duty of HA-CD44
interaction in the development of tissue fibrosis, several research
groups have started to use HA nanoparticles as drug transfer
systems for liver fibrosis [47,96]. CHA drug nanogels show 2-7
times cytotoxicity in CD44-resistant human breast and pancreatic
adenocarcinoma cells in comparison to free drugs and HA-
unmodified drug mixtures, showing that these nanoparticles are
affective via Through endocytosis, they mediate CD44 receptors
and interact simultaneously with the cancer cell membrane [37]
The ability of HA to interact with the underlying layer of the skin
to explain the mechanisms of the properties of increased
penetration was investigated. Low molecular weight HA (5 kg
dalton) can improve intrusion into healthy skin, even
macromolecules such as bovin serum albumin, thanks to
hydration of the stratum corneum, interaction with keratine and
protein transfer with HA. [88,97]. In special, its large molecular
structure and loose HA torsion allow it to act as a shock absorber,
resistance to tissue compacting, and cell trauma. The natural
properties of HA make it a promising candidate as a hydrogel
platform for the transfer of progenitor cells also providing a
matrix for cell growth [42].
2.2 Heparin
Heparin is a sulfated, biocompatible, biodegradable, water-
soluble, natural anionic polysaccharide derived from natural and
consisting of the major repeating units of 2-O-sulfo-L-iduronic
acid, 2-deoxy-2. -sulfamino-6-O-sulfo-α. -D-glucose, β-D-
glucuronic acid, 2-acetamido-2-deoxy-α-Dglucose and α-L-
iduronic acid joined each other via 1 → 4 glycosidic bonds [98].
Heparins function as a adjuster of different proteins, cells and
tissues of the man organs make heparin an essential
macromolecule [99]. It is separated from the pig's intestine, cow's
lungs and cow's intestines [100]. Its biological activity is regularly
related to its high load density, which allows for strong
electrostatic interaction with more than 400 different proteins
[101,102]. And affects countless biological processes [100]. It is
made up of a combination of complex structural polysaccharides
that are synthesized via a class of professional enzymes, including
glycosylated transferase, carbohydrate-epimerase, and
sulfotransferase [100]. Heparin is made by the liver, mucous
membranes, and lungs, is a natural anticoagulant, and has a
molecular weight (MW) of about 7,000-25,000 Da. Heparin is a
pentose by a five-carbon sugar ring in the basic chain [99]. For
many biological processes such as protein binding, anti-
inflammatory and anticoagulant reactions are essential
[100,103,104]. And as a preventative factor for sick persons at
high risk, vein thrombosis [100]. To get better blood circulation
following ischemic hurt, antigenic factors for example fibroblast
growth factor (BFGF), which motivates the formation of new
blood vessels, have been used for therapeutic angiogenesis in
ischemic tissues. Chitosan (CS) / poly (g-glutamic acid) (g-PGA)
nanoparticles of heparin-functionalized nanoparticles (HP-CS / g-
PGA nanoparticles) were prepared for multifunctional delivery of
essential fibroblast growth factor and heparin. Heparin, a
traditionally used anticoagulant, can be released from dissipated
nanoparticles to hold antifactore Xa activity in the blood plasma
after raising the pH from 6.6 to 7.4. The functional delivery Nano
- Carriers essential fibroblast growth factor and heparin may be a
potential therapeutic approach to increase ischemic tissue
regeneration and stopping vascular retrombosis [105]. Heparin be
able to confirm growth factors to forbid them from destroying
with proteases. Electrostatic adsorption among heparin sulfate
residues and amino acids remaining from the growth factor
mainly causes the reaction between heparin and growth factor. In
addition, to control of growth factors heparin-based hydrogels
have a significant function [99,106,107]. The discovery of
heparin has greatly aided local procedures, such as heart surgery
and kidney dialysis [100]. Heparin-containing hydrogels are
widely used in emerging fields and often have excellent
properties, including connecting to growth factors (GF),
anticoagulant activity, anticoagulant and apoptotic effects [99].
Despite more than 80 years of use, heparin is still the best choice
for multiple clinical symptoms due to its rapid anticoagulant
response, prothrombin reversibility, suitable for patients with
renal impairment, and relatively few effects [100]. In
hemodialysis and pulmonary heart bypass, anti-coagulation
should be injected to prevent possible clotting, which may be
caused by contact with blood and synthetic materials [108].
Heparin has a high negative charge due to availability of groups
of sulfonic acid and carboxyl, that lets heparin to have an
electrostatically effect by a lot of proteins like growth factors,
proteases and chemokines. A lot of situation, protein stabilization
or increased desire for cellular receptors is the result of these
interactions. Growth factors Fibroblast growth factor (FGF) and
vascular endothelial growth factor (VEGF) available to use for
design a controlled secretion platform for tissue engineering.
Choose of heparin for a polymer to make scaffolding was studied,
which often uses non-covalent heparin bonding with peptides or
proteins to enhance the assembly of hydrogel networks [99,109].
In special, power of heparin to bind and stabilize the underlying
fibroblast growth factor (BFGF) and its role in helping the
complex with the recipient has attracted much attention due to its
fundamental function in cell proliferation, tissue regeneration and
wound healing [101]. To gain A aimed drug delivery system for
chemotherapy, we synthesized a ligand-mediated drug
nanoparticle vector consisting of folate-bound heparin-based
copolymers. The utilization of heparin-based drug delivery
system is receiving special attention due to the attractive anti-
cancer properties of heparin [110]. Low molecular weight heparin
(LMWH) nanoparticles modified by glycyrrhizinic acid (GA)

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(LMWH-GA) and in addition decorated with lactobionic acid
(LA) (LA-LMWH-GA) as target carriers of hepatocellular
carcinoma (HPC) new to overcome their multidrug resistance
(MDR) doxorubicin (DOX). These nanoparticles carry outed
continuous drug release in vitro and prolonged shelf life of DOX
in vivo [111]. However, dosage should be strictly controlled
because excessive use of heparin may cause of bleeding and use
of the low dose may not intercept clotting for enough. The most
important conflict of heparin is thrombocytopenia caused by
heparin, which may cause to platelet damage with immune
reactions (HIT). Therefore, the development of analytical tools
for rapid monitoring of heparin is need. Usual heparin
measurement tests are partial thromboplastin activation time
(APTT), Anti-10 factor, and thromboblastography. Therefore, we
can see still a strong interest in creating more practical and faster
ways to diagnose heparin [108,112-116]. Heparin is present in the
reaction between inflammatory mediators, proteases and
histamines and inside of granules of our mast cells. Utilization of
heparin about manufacturing hydrogels proves that it is useful for
improving environmental compatibility and effectiveness [99].
Hydrogels can be Choose as carriers of cellular and growth factor
and anticancer. Heparin has the potential to combine with
biological molecules and developed biocompatibility and
effectiveness, raise cellular cohesion, the degradation of cell-
mediated protein, and rich functional groups in heparin, thereby
controlling the loading and release of growth behaviors. Heparin
depends on various growth factors and can separate growth factor
from the extracellular matrix and makes heparin an
interesting nominat for growth factors [99,117]. Heparin
hydrogels have been extensively studied due to the three-
dimensional structures of hydrogels in implant applications,
tissue engineering, biosensors, and drug-controlled diffusion.
Because heparin is made from animal sources, it has supply and
safety problems and clinical restrictions in bleeding and
thrombocytopenia. So, in recent years, polymers and hydrogels
imitating analogous heparin originated from non-animal or purely
artificial origins are extensively studied [99]. One chemical
method for making artificial heparin is imitating the heparin
synthesis inside the body. Artificial heparin would be synthesized
completely pure form under adjusted manufacturing facilities and
eliminated heparin-related concerns with animal sources.
Furthermore, artificial heparin is superior to animal heparin in
that it has medicinal effects, especially for patients with particular
needs [100]. Heparin has been shown to react with thrombin
inhibitors such as antithrombin III (ATIII) [4]. Using catalytic
activity of peroxidase such as gold nanoparticles to detect heparin
colorimetry, so that it is largely speed up by goal heparin at neutral
pH [108,118]. Creating a colored heparin sensor based on the
accumulation of gold nanoparticles (AuNPs) resulting from
polymer nanoparticles [108,119]. The gold nanoparticles used to
detect color without a heparin label are based on the effect of
reducing the color by graphene oxide [108,120]. We sort the
shapes of hydrogels into dimensional hydrogels, including huge
hydrogels, injectable hydrogels, and Nano hydrogels. Next, we
brief the different manufacturing methods for hydrogels,
including chemical covalent bonding, physical composition, and
the combination of chemical and physical interactions. Covalent
bonding involves free radical polymerization of vinyl-containing
components, bond-forming reaction, additional Michael-type
reaction, click chemistry, di-vinyl sulfone cross-linking, shell-
inspired coating, and more. Physical hydrogels are conjugated
with host and guest interaction, electrostatic interaction, hydrogen
bonding, and hydrophobic interaction [99]. Natural hydrogels
were made of natural polymers, including cationic polymers
(chitosan, etc.), anionic polymers (pectin, etc.), neutral polymers
(dextran), and so on. Untile artificial hydrogels are made of
artificial polymers, they covering hemopolymers (polyacrylic
acid) (PAA), etc.), random polymers (PAA-copoly (isopropyl
acrylamide) (PAA-co-PNIPAAm), etc.), block copolymers
(PEG). -b-PAA) and so on [1]. Depending on the network
connection form, hydrogels can be separated into cross-linked
physical hydrogels (electrostatic interaction, hydrogen bonding,
chain interconnection, etc.) and interconnected chemically
connected hydrogels (chemical bond bonding). Hydrogels
(depending on the shape, it can be columnar in the future, in the
form of spongy, fibrous, film, spherical, etc..), injectable
hydrogels (amorphous hydrogels), and micro-hydrogels class.
Depending on the answer of the hydrogels to outside motive, they
be able to divide into traditional hydrogels and stimulus-
responsive hydrogels (pH, temperature, etc.). Depending on the
application, hydrogels can be divided into water-soluble
hydrogels, moisturizing hydrogels, biomedical hydrogels, etc.,
due to good features such as hydrophobicity, biocompatibility,
non-toxicity and biodegradability. Hydrogels have been used in
biomedical fields widely. Various types of natural polymers and
artificial have been used to design hydrogels [99-101]. Heparin is
an assemble combination of heterogeneous polysaccharide sulfate
chains. Heparins physical and chemical properties are based on
the association of multiple techniques, but the benefits of using
complementary methods have not yet been completely elucidated.
Strong HPLC-Anion Strong exchange after enzymatic and
slightly one-dimensional digestion of 1H-13C NMR (HSQC) is
the very common technique for determining the structure of
heparin and provides a combination of its structural blocks. SAX-
HPLC is based on the totally enzymatic break of the sample with
a composition of heparinase I, II and III, followed by the
separation of the resulting di and oligosaccharides by liquid
chromatography. NMR-HSQC analysis is performed on whole
specimens and prepare the percentage of mono and disaccharides
by integrating diagnostic heads [121]. Chitosan has been widely
studied as a genetic drug transmission platform. Although, its
effectiveness is limited by the binding power of DNA and RNA.
In anticipation of a decrease in chitosan load-bearing capacity, we
propose to use including heparin as a competing polyyanin in
polyplexes. We produced chitosan-heparin nanoparticles with a
one-step method for local transfer of oligonucleotides. The size

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of the polypexes related on the mass of the polyanion relative to
the mass of the polyplex. The oligonucleotide release mechanism
was pH-dependent and was associated with polyplex swelling and
polysaccharide network collapse. The inclusion of heparin
releases oligonucleotides from chitosan-based polypexes. In
addition, heparin decrease the toxicity of polyplexes in cultured
cells. The cell absorption of chitosan-heparin polyplexes was
alike to that of chitosan polyplexes, but heparin doubled the
transfection efficiency of polyplexes. The use of small chitosan-
heparin interfering RNA (siRNA) with the aim of silencing
vascular endothelial growth factor (VEGF) was 25% higher in
ARPE-19 cells. Throughout chitosan-heparin polyplexes
demonstrated remarkable getting better in gene secretion within
cells, transfection, and disable of the gene in vitro, offering that
this basic strategy could be achieved using non-viral vectors.
Further improve transmission efficiency [122] Berberine alkaloid
is known to significantly decrease the multiplication of H. pylori.
We are a new nanoparticle vector with a heparin peel for the
delivery of berberine for the treatment of Helicobacter pylori.
Laboratory analysis of drug salvation from nanoparticles showed
that this system is able to control the salvation of berberine in
shamed gastrointestinal dissolution medium, and berberine is not
able to place specific budgets in the intercellular or cytoplasmic
spaces, where H. pylori is located. Took Infection [123].
Figure 2: Pectin and starch Structure [149].
2.3 Pectin
Pectin is a family of plant polysaccharides that makes up about
35% of the primary cell walls in certain species and is structurally
the most complex polysaccharides in nature. The term pectin
actually describes a group of oligosaccharides and
polysaccharides that have common properties, but they are very
different in terms of their very good structure, except that they all
make up at least 65% galacturonic acid (GalA). Which exists in
O. Positions -1 and O-4 are the three well-known main pectic
polysaccharides Pectin, a carbohydrate polymer, has been used to
produce environmentally friendly composite films with excellent
gel formation, degradability, and biocompatibility [124]. Pectin is
a water-soluble acidic hydrochloric acid that is found mainly in
the cell walls of plants and is rich in D-galacturonic acid β- (1-4)
with significant amounts of galactose, arabinose and rhamnose
[125]. Pectin is a complex heteropolysaccharide that contains
spines of α-1,4-galacturonic acids that are somewhat esterified in
carboxylic acid groups. Based on esterified carboxylic acid
groups, pectin is divided into two categories with different
applications: high methoxyl pectin (HMP, ester grade above 50%)
and low methoxyl pectin (LMP, esterification grade below 50%).
The presence of esterified groups as well as neutral sugars as side
chains leads to the formation of several parts covalently to each
other, of which hemogalacturonan, rhamnogalacturonan I and II
and xylogalacturonan are the most important. These
polysaccharides, which are widely distributed in the cell wall of
plant tissues, have many uses in food (as a gel, emulsifier and
stabilizer) and drugs (as an anti-tumor, antioxidant, anti-diabetic
and anti-cancer agent). The pectin structure binds have three
different porous polysaccharides, namely Homo galacturonan,
Ramnogalacturonan (RG-I) and rhamnogalacturonan II (RG-II)
[126]. Hemoglacturonan (HG), 190 rhamnogalacturonan (RG-I),
and rhamnogalacturonan II (RG-II). Among the three
polysaccharides, HG is one of the most abundant, having a linear
homopolymer of α-1,4-linked GalA containing 65% of pectin.
RG-I contains 20-35 Ca pectin ٪ containing the backbone of the
diacarid repeating unit [-α-D-GalA-1,2-α-L-RG-1,4-] n. RG-II
makes up 10% pectin and instead of RG has an HG backbone with
complex side chains attached to GalA residues. RG-II is
structurally the most complex of the three porous
polysaccharides, and the chemical structure of its details has not
been established with certainty, knowing that it is largely
preserved among plant species. Pectin is a heteropolysaccharide
found in the stem cell walls of terrestrial plants. Pectin was first
reported through Henry Braconot in 1825. It is mostly
commercially available in light brown color and is mostly made
of citrus and most foods are used as a yellowish substance, mostly
in jellies and jams. In addition to its applications in the
pharmaceutical industry, pectin has many applications in the food
industry as a food, primarily due to its gel-forming and stabilizing
properties. Traditional uses of pectin in the food industry include
the production of jams and jellies, fruit juices, confectionery
products and bakery fillings. Recently, the emulsion properties of
pectin from specific sources have been extensively investigated
to demonstrate its ability to stabilize oil-in-water emulsions. In
particular, pectin from sugar beet has an exceptional emulsifying
property due to its higher content in the protein and steel groups
compared to pectin from other sources. Some pectins have
significant emulsifying properties such as pumpkin pectin, sugar
beet pectin, citrus pectin, apple pectin [127], Pectin cocoa shells

7. Advances in Applied NanoBio-Technologies 2020, Volume 1, Issue 2, Pages: 33-44
39
[128], pectin pomegranate peel and so on. Traditionally, pectin is
obtained from citrus peels by acidic water, which leads to its
degradation and change in structure and natural properties,
respectively. Therefore, various non-conventional methods such
as microwave extraction, supercritical liquid extraction and
ultrasonic extraction (UAE) extraction have been developed.
Among these methods, UAE destroys the plant's cell wall with the
caviar effect of ultrasonic waves and increases the rate of mass
transfer, which leads to higher efficiency and quality of
recoverable pectin with a shorter extraction time. Also, this
method is a green method due to less consumption of solvents and
energy. Therefore, the UAE can be a good alternative to the
conventional approach. Pectin is used in food packaging as a non-
toxic polymer matrix in the manufacture of edible films used to
increase food safety and increase shelf life. However, high
hydrophobicity and poor mechanical properties of pectin film
limit its use as a packaging material. In order to improve the
properties of biopolymer film, nanomaterial mixing methods such
as metal nanowires, nanoparticles and metal oxides and
nanocellulose have been proposed, which have strong interactions
with polymer matrix to strengthen the properties of the film and
create additional functions. Properties such as antimicrobial
activity and antioxidant activity in some cases [129]. Due to the
quentessential structure of pectin, it can be converted into a
variety of useful products. It can be used as a compound in many
polymers to make a mixture or a composite material. Due to the
significant accumulation in the chemical composition and cross-
linking mechanism, different pectin hydrogels have been
prepared based on different characteristics in pharmaceutical and
biomedical sites. Innovative properties of hydrogels such as
bulking, swelling, solubility and hydrophobicity make them a
better alternative to wastewater treatment. Recently, pectin-based
hydrogels have shown excellent performance in removing ions
and various metal metals from contaminated water. Nanoparticles
can be used to improve the adsorption properties of pectin-based
hydrogels, which leads to the development of hydrogel
nanocomposites. Pectin is a natural polysaccharide in which
pectic acid and some acidic polysaccharide units are partially
methylated to methyl esters. It is easily converted to pectic acid
by saponifying with alkaline groups such as calcium hydroxide.
In plant biology, there is a strong group of polysaccharides in
pectin, which is found in the walls of most primary cells. Extreme
amounts are found in non-woody parts of terrestrial plants. Pectin
is the most valuable constituent of the middle layer, where it
supports to hold cells, but is also present in the starting wall. The
amount of pectin and chemical structures are found separately in
each part of the plant. Pectin is one of the important
polysaccharides in the cell wall that expands the cell wall of the
initiator and commands the plant to grow. During fruit ripening,
pectin is damaged by the enzymes pectinase and pectinestra. In
this biological activity, fruits soften and pectin gives the property
of a kind of soluble fiber. Pectin in fruits and vegetables is related
to the chemical structure and molecular density in the form of
polymolecular and polymorphic. Pectin is a group of substances
that dissolve in water under the right conditions. It is derived from
the protoptin in the middle layers of plant cells. Proteoctin is not
soluble, but when the fruit ripens, it becomes soluble pectin. If
dissolved at high temperatures, single-pot diazonium salts or
alkali metal salts of biting acids are usually soluble only in water
but not in liquids. Diazonium di Valent and three valent salts have
poor solubility and are insoluble [130]. With solubility, the
density of the pectin solution is linked to molecular / atomic
weight, degree of esterification (DE), concentration of the
synthesized solution, pH behavior, and ion expression in the
prepared solution [131]. Typically, density, viscosity, solubility
and gel formation are correlated, e.g. parameters that increase the
volume of the gel, for example, increase the gel capacity, lower
solubility and increase the density / viscosity [132]. All of these
physical properties of pectin are due to their configuration, which
is a double-stranded polyanion (polycarboxylate) [133]. The
maximum stability of pectin is at pH 4. Below and above this pH,
pectin esterification occurs and as a result its stability decreases.
The rate of deionization is higher than the rate of
depolymerization. The presence of solvents, which reduce the
activity of water, slows down both reactions. Depolymerization
occurs by hydrolyzing the acid catalyst of glycosidic bonds at low
pH values. Acid-activated hydrolysis on L-rhamnopranosyl
glycosidic bonds is preferable [134]. Some fungal pectins produce
lm-pectins, which are similar to pectins, which have the ability to
gel with bases and acids and are sensitive to calcium ions. The
fungal pectin esters of Aspergillus japonicas are able to exchange
high methoxyl (hm) pectin in low methoxyl (lm) pectin and are
able to produce strong gels with calcium ions. Pectin estraz
rapidly alters high methoxy pectin to low methoxy pectin under
mild conditions and without polymerization of pectin particles.
Pectin-based materials and pectin have a very high potential and
play an important role in indifferent fields. In pharmacy can be
used as emulsifying, suspending, stabilizing and binding agent.
2.4 Strach
By many plants starch is produced, starch is a natural,
reproducible and degradable polymer, it is a source of stored
energy. This is the second greatest biomass in nature. Amylose
and amylopectin is two glucosidic macromolecules which
composed starch mainly [135]. They are different in terms of
chain structure. Glucose units is made amylose as a linear
molecule, that is mainly bound by α-(1-4) glycosidic bonds, with
an average molecular weight of less than one million [136-139].
Amylopectin, however, is widely associated with α- (1-6) branch
bonds, with a mean molar mass of up to hundreds of millions
[136-140]. Starch Due to its destructiveness, abundance and low
cost, starch is widely used in various applications such as water-
soluble bags for insecticides, engineering scaffolding. Tissue
[141], Stimulants for pills and drug carriers. In addition, partial
hydrolysis (chemically or enzymatically) of low molecular weight

8. Advances in Applied NanoBio-Technologies 2020, Volume 1, Issue 2, Pages: 33-44
40
starch or glycogen products, dextrin polysaccharides, is now
widely used in biomedical applications [142]. Most starches are
domestically restricted, such as high viscosity, re-sensitivity,
limited digestibility for some, and limited solubility for others.
For this reason, the starch used in food or industrial applications
is first modified [143,144]. Starch has been chemically and / or
physically modified to enhance its positive properties, reduce its
undesirable properties (such as high viscosity, sensitivity to re-
administration, and process intolerance), or add new properties
(Retention, film formation, digestibility, solubility, etc.). In fact,
mild hydrolysis of acid has long been used to modify starch and
its properties. In industry, starch slurries are treated for various
periods of time with diluted HCl or H2SO4 at 55-55 C to produce
acid-modified starch, which, as a size material, is used in the
production of gum sweets. Paper and paper production is
produced. Recent publications use both acids to make starch
nanocrystals [143]. As a degradable and non-toxic polymer, starch
is widely used in Non-food applications such as articles, fabrics,
plastics, cosmetics and pharmaceuticals are used [145]. Recent
studies have reported that nanoscale starch particles can be easily
obtained from starch grains, which have unique physical
properties. Because starch is environmentally friendly, starch
nanoparticles are recommended as one of the most promising
biologics for new uses in food, cosmetics, medicines, and a
variety of composites [146]. Studies show that tooth decay has
recently become widespread. Starch containing curcumin can act
as an alternative to preventing the activity of Streptococcus
mutans attributed to biofilm and plaque formation on teeth. In this
study, the performance of starch nanoparticles as a carrier of
curcumin, a natural anti-inflammatory and a powerful antioxidant
in reducing tooth decay, was simulated [147].
3 Vision and Conclusion
Polysaccharide-based nanoparticles are of great importance as
transmitters of various drug agents due to their physicochemical
and biological properties. As a result, researchers have used
polysaccharide-based (or polysaccharide-derived) nanoparticles
to combine the nature of different mechanisms (e.g.
polyelectrolyte complex (PEC)), self-assembly, covalent cross-
linking, and ion cross-linking. It depends on the substance. Most
polysaccharide-based (or derived polysaccharide) nanocarriers
have low protein reactivity and mobility. This behavior, in
addition to their natural inherent properties such as
biodegradation and biocompatibility, makes polysaccharide-
based nanocarriers a high-potential substrate for DDS
development. In summary, the use of polysaccharide-based
nanogels in the human body or in vitro to deliver a variety of
pharmacological agents to the site of cancerous tumors is a future
exploratory field of research.
Ethical issue
Authors are aware of, and comply with, best practice in
publication ethics specifically with regard to authorship
(avoidance of guest authorship), dual submission, manipulation
of figures, competing interests and compliance with policies on
research ethics. Authors adhere to publication requirements that
submitted work is original and has not been published elsewhere
in any language.
Competing interests
The authors declare that there is no conflict of interest that
would prejudice the impartiality of this scientific work.
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