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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5604_Библиотеки_им_академика_М_И_Перельмана.pdf
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 195
intriguing possibility for medication delivery systems because of the numerous effective drug delivery-related characteristics. CNOs can be functionalized with different
pharmacological compounds or targeted ligands due to their high surface area. It can
also encapsulate pharmaceuticals inside their layers, guarding against their premature release and deterioration. The therapeutic competence of drug may be enhanced
by this regulated release. Moreover, by affixing targeting ligands or antibodies to
their surfaces, functionalized CNOs may be made to target certain cells or tissues.
This may improve drug delivery’s precision and lessen off-target effects. In addition
to this, biodegradability, biocompatibility, non-toxic and its stability helps CNO for
effective controlled drug delivery [44–48].
1.2.5 Nanodiamond
With particle sizes of up to 5 nm, ND is the most stable carbon compound. Like every
solid particle, a ND particle is made up of a single-crystal diamond core encased in
a shell, or “coat,” of functional groups [49]. Because of their desirable qualities such
as their substantial diameter, excellent thermal conductivity, durability, resilience to
friction, non-toxic nature, small and adjustable structural properties of surface, large
surface area, chemical inactivity, and outstanding optical and mechanical properties,
ND is now the focus of active research. Quantum optics, fabrication of coatings for
bactericidal activity, antifriction characteristics, electrochemical action, probes for
bioimaging, polymer reinforcing agents, catalytic platforms, polishing and lubricants
agents, as implants, and in water decontaminating process and medication administration procedure are just a few of the applications that have been made possible by
these special qualities of ND [50].
1.2.6 Carbon Quantum Dots
CQD is a fluorescent 0D carbon nanostructure with dimensions less than 10 nm.
This nanomaterial has garnered increased interest in recent years owing to their
qualities like tiny size, fluorescence emission characteristics, chemical robustness,
water-soluble properties, ease of production, and modification capability. Compared
to heavy metal semiconductor quantum dots (QDs), fluorescent CQDs are with
minimal noxiousness and excellent physicochemical features, making them the ideal
candidates for biomedical applications [51]. CQDs have become a popular alternative for serving as nanocarriers for medicines, photosensitizers, and bactericidal
components in a variety of biomedical applications. Their capabilities have also
been demonstrated in fabrication of multipurpose diagnostic systems, cellular and
microbe bioimaging tools, and theranostics nanomedicine [52]. Bioimaging, medication delivery, gene delivery, and cancer treatment are some of the biological uses
of CQDs. In addition to this, CQDs can be used as nanocarriers for medication and
196 K. M. Sahu et al.
tracking and delivery agents for gene. Beyond their roles as medication administration vehicles and fluorescent tracers, CQDs have demonstrated the ability to regulate
drug release.
1.3 Polysaccharide-Based Nanocomposite
The polymeric matrix and additives with a minimum of one dimension in the
nanoscale spectrum are combined to form a polymer nanocomposite. In general,
there are three main classes of additives or fillers based on their dimensions (0D,
1D, and 3D) [53]. For the case of polymeric matrix, it may be natural, synthetic,
or biopolymers. In recent times, biopolymers have gained significant popularity as
polymeric matrix to form nanocomposite. Biopolymers fall into three main families: polysaccharides, proteins, and nucleic acids. Polysaccharides include several
distinct characteristics that set them apart from other families of biopolymers. They
are encompassed of several saccharide units associated with each other via glycosidic
bonds. The majority of polysaccharides are readily and affordably recovered natural
compounds that are produced by microorganisms, plants, and animals as structural
or energy-storing biopolymers. In terms of materials science applications, polysaccharides are superior to proteins and nucleic acids in a number of ways. Compared
to proteinaceous compounds and nucleic acids, polysaccharides are typically more
stable and do not undergo irreversible denaturation when heated. Polysaccharides
come in a broad range of properties, such as low, intermediate, and high molecular
weights with varying polydispersities. They can be monofunctional consisting of
specifically hydroxyl group or polyfunctional containing hydroxyl, carboxyl, and/
or amino groups. Additionally, polysaccharides exhibit magnificent chiral properties, water-soluble or insoluble qualities, low toxicity, environmental safety, and
non-immunogenicity [54]. Several well-known polysaccharides with a wide range
of biological uses include chitin, chitosan (CS), cellulose, agarose (AG), starch,
hyaluronic acid (HA), guar gum (GG), alginate (ALG), pectin, and dextran (dex).
The functionality of polysaccharide-based matrixes is improved, and their application window is expanded, by the integration of nano-ranged materials with a large
specific surface area and advantageous intrinsic features [55]. Polysaccharide-based
nanocomposites have been tremendously implemented in biomedical applications
owing to their diverse range of characteristics such as capability to interact with
biomolecules, non-toxic nature, and biodegradable ability.
The present chapter delves into the intricate landscape of drug delivery characteristics and functionalities associated with CNs such as CNT, graphene, CNH,
CNO, ND, CQD, and polysaccharides, namely ALG, cellulose, CS, Dex, starch,
HA, pectin, GG, AG, carrageenan, and glucomannan (GM). In addition, this chapter
painstakingly discusses the effective amalgamation of polysaccharides with a wide
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 197
range of CNs. This integration is not only explored with regards to synthesis methodologies but also in concern with how it enhances the overalldrug deliveryfunctionalities of the resulting polysaccharide-based nanocomposites. Furthermore, the efficacious results in the area of drug administration via CN-incorporated polysaccharidebased nanocomposite are also scrutinized in this comprehensive exploration. Moreover, it not only sheds light on the individual properties of these materials but also
explores the synergies that arise from their combination, offering valuable insights
for researchers, scientists, and practitioners within the domain of nanomedicine and
medication delivery.
2 CN-Incorporated Polysaccharide-Based Nanocomposites
for Drug Delivery Applications
2.1 CN-Incorporated Alginate-Based Nanocomposite
ALG or alginic acids are unique among seaweed hydrocolloids owing to their derivation from brown seaweeds. Within brown seaweeds, ALG serves as a fundamental
constituent of cell walls and is also found in the intercellular space matrix. This
suggests that ALG ubiquitously are present in the majority of brownseaweed species.
The primary species utilized for the commercial extraction of ALG include Laminaria
spp. and Macrocystis spp. However, ALG is generally derived from Ascophyllum
spp., Sargassum spp., and Fucales spp. In addition to this, it is also obtained from
bacteria, including Azotobacteria and Pseudomonas. It is worth noting that these
bacteria-containing linear polymers are constructed from two distinct monomers
of uronic acids, i.e., β-d-mannuronic acid (M) and α-l-guluronic acid (G). These
two uronic acids are aligned in an inconsistence block-wise pattern, with a diverse
range of proportions of MM, MG, and GG blocks. The specific composition of
these blocks depends on factors such as the algal source, derivation method, and
harvest time. Mannuronic acids are linked through β-1,4 linkages, resulting in a
linear and flexible conformation for the MM blocks. In contrast, guluronic acid
is connected through α-1,4 linkages and is responsible for the steric hindrance in
the vicinity of carboxyl groups present. This structural feature creates a folded and
rigid configuration within the GG blocks, ensuring the creation of stiffness within
polymeric chain. The combination of these different block types contributes to the
unique properties and versatility of ALG [56]. ALG has garnered extensive attention
and found widespread use in various biomedical applications owing to its desirable
qualities, including biological compatibility, less noxiousness, cost-effectiveness,
and mild gelation ability when exposed to divalent cations like Ca
resemblance of hydrogels made from ALG with the extracellular matrices of living
tissues enables a broad spectrum of applications, including wound dressing, cell
transplantation, and regulated release of biologically active components like minute
chemical medications and proteins. ALG-based wound dressing materials maintain
2+
. The structural
198 K. M. Sahu et al.
a physiologically moist microenvironment, which promotes efficient wound healing,
minimizes the risk of bacterial infections, and accelerates the recovery process. This
makes ALG a potential polysaccharide to be utilized in the biomedical field [57].
Owing to the above-said characteristics of ALG, researchers are keen to investigate not only pristine ALG but also the nanocomposite made from ALG and
CNs in therapeutic administration applications. Cui et al. engineered sodium ALGfunctionalized nanodiamonds (fNDs) system for drug delivery.The functionalization
of NDs with sodium ALG induced a transformation in the sharp surface of the ND
particles, causing it to become blurred, which helped in converting ND a suitable
drug administration CN. In this experimental work, cisplatin, a representative drug
model, was coated onto the negatively charged fND clusters. Complexes of fNDs
and cisplatin were established through multivalent anionic interactions between the
fND and cisplatin. Their study revealed that fNDs effectively increased therapeutic
accumulation and prolonged persistence time within tumour cells. Consequently, this
enhanced medication delivery strategy resulted in a sustained cellular toxicity effect
on tumour cells even after the completion of the drug treatment period. Schematic
demonstration of enhanced therapeutic accumulation and retention in tumour cells
by sodium-ALG functionalized fND is presented in Fig. 1 [58]. Majumdar et al.
successfully created a stimuli-responsive smart therapeutic delivery system designed
to release drugs under the influence of the local environment, specifically the concentration of pathogens present. The chosen drug deliverysystem (DDS), calcium ALGcarbon dot (CA-CD), was employed alongside garlic extract (GE), containing Allicin
as a model therapeutic to validate the proof of concept. This distinctive medication
administrativeplatform not only demonstrated stimuli responsivenessbut also served
as a controlled drug release mechanism, responding to variations in cell concentration. The interdependence of medication release, cell concentration, and the pH of
the medium was noteworthy. As cells divide, they produce secondary metabolites,
leading to a reduction in the pH of the administration medium. This drop in pH
value activates the drug administration process from the beads, and the subsequent
impact of the drug is evident in the resulting MRSA cell death. The ability of this
kind of advanced smart drug delivery vehicles to adapt and respond to specific environmental cues, namely pH and pathogen concentration, opens avenues for targeted
and efficient drug administration with potential applications across various biomedical contexts. Figure 2 displays schematic representation of the adopted protocol for
studying in vitro drug release by the CA-CD-GE bead [59]. Some CN/Alginate-based
therapeutic delivery vehicles are summarized in Table 1.
2.2 CN-Incorporated Cellulose-Based Nanocomposite
Cellulose, a crucial polysaccharide found abundantly in plants, represents an
abundant and versatile source of polymeric raw materials. It stands out for its
hydrophilicity, chirality, biodegradability, broad spectrum of chemical modification
possibilities, and its ability to produce a variety of semicrystalline fibre structures
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 199
Fig. 1 Schematic demonstration of enhanced therapeutic accumulation and retention in tumour
cells by sodium-ALG functionalized fND. Reproduced with permission from Elsevier [58]
Fig. 2 Schematic representation of the adopted protocol for studying in vitro drug release by the
CA-CD-GE bead. Reproduced with permission from ACS [59]
[65]. Owing to non-deleterious, biodegradability, and biocompatibility characteristics, cellulose serves as a valuable nonviral vector. It predominantly manifests as a
linear homopolymer composed of glucose (C
)n, where the variable n ranges
6H10O5
from 500 to 5000. Cellulose is the paramount prevalent polymeric substance, characterized by repeating constituents connected by 1,4-β glucosidic linkages [66]. It is
non-toxic, biodegradable solids with molecular masses ranging from 1.44 × 10
6
to
Tabl e 1 CN-incorporated alginate nanocomposite-based drug delivery vehicles
Sl. No CN/Alginate-based
Drug model Characterization Stimuli responsiveness Drug release References
drug delivery vehicle
1 Fe3O4@SiO2@al/
CQDs
2 D-Biotin/DOX-loaded
mPEG-OAL/N-CQDs
Doxorubicin
(DOX)
XRD, FTIR, VSM, UV-Vis,
AFM, TEM, FESEM, PL
Doxorubicin hydrochloride1H NMR, TEM, PL, FTIR,
UV-Vis, Confocal
microscopy
3 CA-CD/β-TC Tetracycline hydrochloride FTIR, TGA, SEM, TEM,
PL, Zeta potential
4 CA/SWCNT -Gl Curcumin
(CUR)
FTIR, XRD, SEM, EDX,
TEM, DLS, TGA
5 GO-CS/SA DOX FTIR, AFM, Zeta potential,
TGA, Fluorescence
pH Time
%
(h)
pH 5.5 48 38 [60]
7.5 48 25
pH 5.0 24 65.6 [61]
6.5 32.3
7.4 –
pH 1.0 96 61 [62]
pH 4.5 96 – [63]
7.5
pH 5.0 120 51.6 [64]
7.4 31.6
200 K. M. Sahu et al.
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 201
1.8 × 106g/mol. They exhibit remarkable thermal stability and undergo thermal softening at temperatures ranging 231–253 °C. Pure cellulose offers excellent resistance
with low conductivity. Among all polysaccharides, cellulose has garnered significant attention from myriad research groups due to its sustainability, distinctive
morphology, high crystallinity, ample specific surface area, favourable rheological
characteristics, liquid crystalline behaviour, unique alignment and positioning characteristics, mechanical reinforcement capabilities, barrier characteristics, chemical
reactive nature of surface, biocompatible capability, minimal cytotoxicity, exceptional mechanical attributes, and biodegradability [67]. Along with this, cellulose
has gained attention for its potentiality to interact and make intricate nanocomposite
with various nanomaterials, specially with CNs to generate drug delivery systems.
Luo et al. aimed to produce transparent and porous NDs/cellulose nanocomposite
membranes for controlled administration of DOX. Their ultimate goal was to explore
their competence applications as advancedwound dressings. By comparing the medication release profiles of these membranes at pH 7.4 and pH 5.5, it was observed that
membranes demonstrated a notably increased release of DOX at pH 5.5 in contrast
to the release observed at pH 7.4. In this case, the observed sustainable release can be
ascribed to several factors. Firstly, the prolonged release is influenced by the deeper
entrapment of DOX which is necessary for the drug molecules to travel the greater
distance during the release process. Secondly, the electrostatic interaction present
among the carboxyl groups of carboxylated ND (CND) and the amine groups of
DOX weakens the strength of interaction between DOX adsorbed on the surface of
CND nanoparticles. Furthermore, the sustained release phenomenon is influenced
by the improved solubility of DOX in acidic pH [68]. Mianehrow et al. designed
a nanohybrid (rGO-CS-HEC) therapeutic administration system to carry folic acid
(FA), as model drug. The interaction among the CS, hydroxyethyl cellulose (HEC),
and rGO present in the nanohybrid structure and association of FA with the carrier
by the help of hydrogen bonding and π–π interactions during the loading procedure
are illustrated in Fig. 3. They compared the release profile of FA from rGO-CSHEC, rGO-CS, and rGO-HEC at pH 5.3. After the careful evaluation of drug release
data, they concluded that rGO-CS-HEC released 27% of loaded drug in 120 h which
was higher in comparison to the release % of FA from rGO-CS and rGO-HEC.
As a controlled drug administration carrier with biocompatible nature, rGO-CSHEC can be a favourable alternative for many medication delivery platforms [69].
Table 2 provides an overview of drug administration vehicles that originated from
CN/cellulose for the delivery of drug models such as CUR, ibuprofen, quercetin, FA,
and DOX.
2.3 CN-Incorporated Chitosan-Based Nanocomposite
The deacetylated form of the natural polymer chitin, known as CS, was first discovered and discussed by Rouget in 1859. This naturally occurring linear polysaccharide,
202 K. M. Sahu et al.
Fig. 3 Pictorial demonstration of synthesis of rGO-CS-HEC and loading of FA on rGO-CS-HEC.
Reproduced with permission from Elsevier [69]
CS is mostly made up of β-(1,4)-linked glucosamine units (2-amino-2-deoxy-β-Dglucopyranose) and a small number of N-acetylglucosamine units (2-acetamino2-deoxy-β-D-glucopyranose). Biocompatibility, biodegradability, and non-toxicity
are some attributing properties of CS. Among many other industrial applications, its
remarkable biological properties like bactericidal activity and coagulating characteristics, bioadhesive nature, and wound closure ability position it as an outstanding
choice for incorporation into cosmetics, pharmaceutics, and food industries, safeguarding of agricultural commodities, and waste water decontamination procedure.
CS displays solubility in weak solutions of various organic and inorganic acids (with
a pH less than 6) because its amino groups get protonated under the influence of
pH variations. Although CS is not commonly found in nature, it can be located
in certain fungi belonging to the Mucorales order, specifically within the Mucor,
Absidia, and Rhizopus species. Commercially,CS is predominantly derived from the
extensive deacetylation of its precursor polymer, chitin. The deacetylation process
for chitin to yield CS typically involves the hydrolysis of acetamide groups using
concentrated NaOH or KOH solutions (at concentrations of 40–50%) at temperatures
exceeding 100 °C. This chemical reaction is usually conducted in the environment
where the components are not uniformly mixed. The molecular weight (Mw) of CS
can vary from 300 to more than1000 kD, and its degree of deacetylation ranges
from 30 to 95%, depending on the synthesis method and their sources. CS was first
primarily employed in medical applications, such as tissue engineering, slimming,
and wound dressing. Nevertheless, over time, CS emerged as a leading contender for
drug delivery systems. Its remarkable biological activity and biodegradability, along
Tabl e 2 CN-incorporated cellulose nanocomposite-based drug delivery vehicles
Sl. No CN/Cellulose-based drug
Drug model Characterization Stimuli
delivery vehicle
1 rGO-CS-HEC FA UV–Vis, Zeta
potential, FESEM,
DLS
2 CMC1@MWCNTs@FCA CUR FTIR, XRD,BET,
SEM. EDX
3 CMC1/MG@mSiO2-IBU Ibuprofen FTIR, XRD,BET,
SEM. EDX,DSC,TEM,
VSM, Zeta potential
4 CS/CMC1/CNTs/QC Quercetin FTIR, XRD, FESEM,
Zeta potential, DLS,
UV–Vis,
5 CMC1/GQD DOX FTIR, XRD,SEM,
TEM, UV–Vis, DLS
responsiveness
pH Time %
pH 5.3 120 h 30 [69]
pH 1.2 – 11.6 [70]
7.4 – 76.5
pH 7.4 480 min – [71]
pH 5.4 96 h 97 [72]
7.4 57
Drug release References
pH 4.5 – Lower drug
7.4
release in
acidic pH
[73]
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 203
204 K. M. Sahu et al.
with its antibacterial action and low immunogenicity, created enough opportunity
for its advancement in several domains. CS’s amine functional group is responsible
for a number of important biological characteristics, including mucoadhesion, regulated drug administration, transfection, in situ gelation, permeability improvement,
colon targeting, and efflux pump inhibition [74, 75]. It demonstrates several advantageous properties as a safe and biodegradable platform for therapeutic administration.
The release of small drug molecules from CS composites occurs through various
mechanisms, encompassing diffusion, swelling, erosion, and biodegradation [76,
77]. However, the drug release behaviour is also contingent on its physical proper-
ties, including size, dose, hydrophilicity, and hydrophobicity [78]. To make CS more
viable in therapeutic administration, CNs have been incorporated to prepare CN/CS
nanocompsoite systems. Out of various CNs, fullerene is also a tremendously known
CNs in biomedical applications. Sukhodub et al. designed a bioactive nanocomposite
drug administration vehicle in the form of beads for the release of hydrophobic drug
by utilizing microwave irradiation. This bioactive nanocomposite (HA
-CS-C60)isa
1
3D matrix which composed of CS which is crosslinked via sodium tripolyphosphate
with HA, and C
particles are distributed within the matrix. The drug release study
60
revealed that the developed bead showed the sustained release of Anaesthesinum up
to 18 days. They have also concluded that by varying the concentration of C
60
,the
release rate kinetics can be seen close to zero order kinetics release profile. Preparation, drug release, and bone tissue repair process and antimicrobial mechanism of
-CS-C60are illustrated in Fig. 4 [79]. Another drug delivery carrier for effective
HA
1
administration of DOX was fabricated by Chen et al. In the first step of preparation,
DOX loaded with SWCNHs is developed and in subsequent steps, DOX-SWCNH
is functionalized with DCA-HPCHS to enhance the biocompatibility of the carrier
system in different physiological conditions. The model drug DOX is loaded onto
the SWCNHs via p–p stacking interaction. The as-synthesized material is a multifunctional carrier for the healing process of cancer through photothermal heating in
both in vitro and in vivoprocess [ 39]. Different CN-incorporated CS nanocompositebased drug delivery vehicles along with the model drugs used for the administration
process are comprehended in Table 3.
2.4 CN-Incorporated Dextran-Based Nanocomposite
Dex is a naturally occurring polysaccharide that is highly hydrophilic and biocompatible. It is mostly comprised of uninterrupted sequential chains of α-1,6 linked
glucopyranose units and is extensively employed in medicine [82]. The presence
of α-1,6 glycosidic bonds, which increases chain mobility, is responsible for Dex’s
solubility in a range of solvents, including water, DMSO, ethylene glycol, and glycerol. Louis Pasteur discovered Dex in 1861 from bacteria that produced slime; these
bacteria were subsequently termed Leuconostocmesenteroides by van Tieghem in
1878. Later research has demonstrated that a number of facultatively anaerobic grampositive cocci, including strains of Streptococcus and Leuconostoc, may generate