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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5362_Библиотеки_им_академика_М_И_Перельмана.pdf
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 205
Fig. 4 Preparation, drug release, and bone tissue repair process and antimicrobial mechanism of
HA-CS-C
. Reproduced with permission from Elsevier [79]
60
Dex. The type of bacterial strain that produces Dex determines the degree and kind
of branching units at positions 2, 3, and 4. In the natural world, dextransucrase, a
lactic acid bacterium enzyme, catalyses the conversionof sucrose’s d-glucopyranosyl
residues to Dex which is how most extracellular Dex is made. To create colloid
osmotic pressure which allows fluid to be drawn from the interstitial space and
into the plasma, Dex substitutes blood proteins like albumins. By lowering blood
viscosity and preventing erythrocyte aggregation, Dex 40 can increase blood flow.
As a biopolymer, Dex offers several benefits including high solubility, biocompatibility,biodegradability, and non-immunogenicityfor creating drug-delivery nanoparticles [83]. A novel dual drug-loaded system was engineered with the assistance of a
layer-by-layer self-assembly method, from anionic GO, cationic polyethyleneimine,
and poly-anionic dextran sulphate (GO/PEI/DS). The fabrication of this dual drugloaded carrier aimed to augment the transdermal administration of anti-cancer drugs.
After the oral administration, the average duration of drug residence in the bloodstream was 83.98 ± 3.71 h, whereas with the transdermal route of transportation of
therapeutic, the drug residence time extended up to 149.62 ± 6.11 h. Rajeev et al.
conducted in vivo pharmacokinetic investigations on Wistar rats which involved
both oral and transdermal administration routes. It was observed that the transdermal delivery of the dual drug-loaded material led to a sustained and extended
period of availability of the drugs in the bloodstream. The results revealed that the
developed dual medication-loaded carrier demonstrated pH-tailored controlled and
sustained administration profile for both DOX and MTX when administered transdermally, in contrast to oral delivery [84]. Hu et al. engineered rGO nanoparticles by
employing Dex as a reducing components. In this approach, Dex was forthwith linked
to rGO through hydrogen bonds and subsequently self-assembled to generate rGO/
Dex nanoparticle. Addition of rGO with Dex not only enhanced the biocompatibility
of resultant material but also effectively improved the accommodation capacity of
the anticancer drug, DOX. The fabrication r oute of rGO/Dex and accommodation
of DOX within rGO/Dex are displayed in Fig. 5a. Incorporation of an oligopeptide
Tabl e 3 CN-incorporated CS nanocomposite-based drug delivery vehicles
Sl. No CN/CS-based drug
Drug model Characterization Stimuli
delivery vehicle
1 HA1-CS-C60beads Anaesthesinum XRD, FTIR, HPLC,
TEM, SEM
2 5-FU-CS-CQD-Apt 5-FU SEM, Zeta potential,
FTIR, XRD
3 DOX-SWNH/
DCA-HPCHS
DOX Fluorescence, flow
cytometry, confocal
microscopy
4 MWCNTs/
gelatin-chitosan
5 CS/TPP/GO Sumatriptan
Ciprofloxacin SEM, FTIR, ATR-IR,
TGA, UV–Vis, EDX
SEM, TEM, AFM,
succinate
TGA, XRD, FTIR,
EDS, DLS
responsiveness
– – up to
pH Time %
– [79]
18 days
pH 5.4 24 h 71 [80]
7.4 24 h 23
NIR irradiation – – – [39]
pH 7.4 90 min 98 [26]
Drugr References
pH 1.2 – More
7.4
substantial
release at 7.4
[81]
206 K. M. Sahu et al.
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 207
Fig. 5 a Fabrication path of rGO/Dex and accommodation of DOX within rGO/Dex and b comparative analysis of cellular uptake capacity of rGO/DOX/Dex, free DOX, and rGO/DOX/RDex.
Reproduced with permission from Elsevier [85]
(RGD) with rGO/DOX/Dex (rGO/DOX/RDex) elevates the intracellular uptake. The
comparative analysis of cellular uptake capacity of rGO/DOX/Dex, free DOX, and
rGO/DOX/RDex via confocal fluorescence images is represented in Fig. 5b. The
proficient cellular uptake and internalization indicate the capability of rGO/DOX/
RDex to enhance targeted cellular absorption, leading to increased intracellular drug
accumulation [85]. Several therapeutic administration vehicles based on CN/Dex
along with the model drug, drug release time, and release % are detailed in Table 4.
2.5 CN-Incorporated Hyaluronic Acid-Based Nanocomposite
HA, alternatively designated as hyaluronan, is a non-sulphated, anionic glycosaminoglycan (GAG) that is widely distributed in connective and epithelial tissues. An individual weighing 70 units on average has around 15 g of HA in their body, of which
33 g are spun over (degraded and synthesized) per day. The building blocks of HA
Tabl e 4 CN-incorporated Dex nanocomposite-based drug delivery vehicles
Sl. No CN/Dex-based drug delivery
vehicle
1 rGO/DOX/Dex DOX FTIR, Raman spectra, XPS,
2 GO-CS/Dex DOX FTIR, AFM, TGA, Zeta
3 GQDs-Dex/PNIPAM Buprenorphine DLS, XRD, PL, TEM, SEM,
Drug model Characterization Stimuli responsiveness Drug release References
pH Time %
pH 5.3 38.4 [85]
TGA, TEM, DLS, UV–Vis,
CLSM, FCM
6.8 48 h 12.7
7.4 7.4
pH 5.0 120 h 49.1 [86]
potential, Fluorescence
spectra
7.4 28.9
Temperature – 7days – [87]
Raman spectra
4 GO-DEX-Apt-CUR CUR FTIR, UV–Vis,1HNMR,
FESEM, AFM, TGA, DLS,
EDX
pH 5.5 2days 70 [88]
7.4 20–30
5 GO-IONP-CS/DEX DOX TEM, AFM, Zeta potential pH 5.0 168 h 59.20 [89]
7.4 36.49
208 K. M. Sahu et al.
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 209
are D-glucuronic acid and N-acetyl glucosamine groups assembled into an energetically stable oligosaccharide by means of β-1,4 and β-1,3 glycoside bond exchange.
These distinct disaccharides combine to generate a coiling chain structure that can
have lengths up to 10 nm and relative molecular masses between 10 and 1000 kDa.
Because of its wide range of molecular weights, HA has developed a variety of elastic
qualities that it may use for a range of therapeutic applications. Human tissues have
HA half-lives that vary from approximately one day in the epidermis layer to up
to seventy days in the vitreous body of the eye [90]. Over the past few years, HA
has been employed frequently in the areas of medication development, surgery, and
the treatment of arthritis. It has recently gained popularity in medication delivery
studies. The key benefits of using HA and its derivatives as sustainable administer
drug carriers are its high viscoelastic nature, plasticity, non-immunogenic property,
strong biocompatibility, and decomposability. Certain tissues, including the liver,
kidney, lymphatic arteries, and the majority of tumour tissues, haveabundant expressions of cell surface specialized receptors, which HA and its derivatives may bind
to selectively. Their particular affinity to their receptors may be the basis for HA’s
targeted administration of medication. Anticancer medicines, proteins, peptides, and
nucleic acids can all be delivered via HA and its derivatives [91]. In addition to this,
unification of HA with CNs has achievedgreat importance in medicinal applications.
A brief summary showcasing different drug delivery platforms based on CN/HA is
included in Table 5.
The dual stimuli responsive C
@CTAF/DNA/HA-SS-COOH nanovehicle was
60
designed by Wang et al. to efficaciously integrate the characteristics of both
magnetic and glutathione (GSH) reductivesensitivebehaviours. The inclusion of both
deshielding and target-specific functionalities in the reduction responsivedisulphidemodified HA-SS-COOH enveloping on C
@CTAF/DNA complexes aims to alle-
60
viate accumulation and control the surface anatomy of the complexes. Complexation
with HA-SS-COOH enables a responsive behaviour to mimic a reductive extratumoral environment. Systematic breaking of disulphide linkages in HA-SS-COOH
by glutathione (GSH) achieves this responsiveness, enabling localized medication
delivery to HepG2 cells. This innovative approach allows precise control over drug
delivery, resulting in a more intelligent and potent targeting mechanism. Figure 6
depicts reduction-sensitive behaviour of C
@CTAF/DNA/HA-SS-COOH [97].
60
2.6 CN-Incorporated Starch-Based Nanocomposite
One of the most prevalent naturally occurring polysaccharides, starch is a semicrystalline homopolysaccharide made up of chains of amylose and amylopectin that
is utilized extensively in the food and pharmaceutical sectors [98]. Starch is the most
prevalent carbohydrate in the human diet and is a polymer of glucose monomeric
units bound by glycosidic linkages. In nature, starch is mostly used as an energy
store. Starch’s abundance, affordability, biocompatibility, and regenerative quality
have made it one of the most optimistic biomaterials for a range of biomedical and
210 K. M. Sahu et al.
Fig. 6 Schematic demonstration of reduction responsive behaviour of C60@CTAF/DNA/HA-SS-
COOH. Reproduced with permission from ACS [97]
industrial uses in recent times [99]. To make the material biodegradable in nature,
starch is utilized as an active ingredient and binder. The factor influencing starch’s
binding ability is the granule surface’s porosity and how it interacts with amylase.
The binding capability of starch with an underlying material is attributed to the
disruption of the crystalline structure within the starch granules. Therefore, when
starch and underlying material are bound together, the substance is more biodegradable when it is hydrolysed by the carboxymethylation process [100]. Starch-based
biopolymers are an appealing and useful class of biodegradable biomaterials due to
their low cost of raw ingredients and their simplicity of processing with either standard plastic processing equipment or basic equipment. Amidst the scarcity of oil and
the increasing awareness of the environmental issues linked to the widespread usage
of polymers generated from petrochemicals, there is a significant push towards the
development of starch-based biodegradable materials for both functional and general
purposes. Also starch-based biopolymers can be used as practical biomaterials such
as transdermal drug deliverypatches, carriers for drug delivery,and bandages for open
wounds. However, because of their severe brittleness and innately low water resistance, they have limited uses. With an aim to alleviate their physical properties and
use, a number of investigationsand techniques have been attempted, including mixing
starch with compounds produced from petroleum, incorporating functional plasticizers, crosslinking through chemical agents, heat treatment, or photoirradiation, and
employing nanocomposites [101]. Some of the starch-based nanocomposite made
from starch and CNs which helps in overcoming the drawbacks of pristine starch are
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 211
concisely explained in the following section. A biocompatible and pH stimuli responsive drug carrier platform was developed by Pooresmaeil et al. by integrating CMS,
GQDs, and Bio-MOF(Zn), to promote the co-delivery of CUR and DOX. Photoluminescent characteristics of GQDs, biocompatibility of carboxymethyl chitosan
(CMS), and porous structural features of Bio-MOFs have jointly inspired to fabricate
the therapeutic delivery carrier. According to BET assessment, the diameter of pore
size of the Bio-MOF(Zn)@CMS/GQDs was found to be around 4.5 nm. The larger
pore diameter contributed to a higher loading of both the drugs. In the in vitro therapeutic accommodation analysis, the loading % for CUR and DOX was calculated
to be approximately 54.2% and 43.2%, respectively [102]. In another therapeutic
release study, a green synthesis procedure was adapted to prepare nanocomposite
hydrogel by utilizing CMC, starch, and rGO. These hydrogels were subsequently
accommodating the dual nanoemulsions, functioning as pH-responsive administration systems for CUR. It was revealed a more rapid release of CUR at depreciated
pH levels. The MTT assay unveiled that higher level of toxicity is possessed by the
nanocomposites against MCF-7 cancer cells in comparison to CMC, CMC/rGO, or
CUR. Nanocomposites exhibit significant promise as drug carriers for the treatment
of terminal cancers, demonstrating the potential for effective therapeutic outcomes
with minimal adverse effects [103]. Pooresmaeil et al. used NAP@GQDs@BioMOF(Cu) to coat carboxymethyl starch (CMS) and CS-based polymeric matrix to
developa therapeutic carrier for Naproxen (NAP). The release results of NAPindicate
that CMS@CS provides gastric prevention and serves as a more s uitable drug carrier
for targeting the colon. Figure 7 represents the synthesis procedure of CMS@CS/
(NAP@GQDs@Bio-MOF(Cu)). It has the potential to f unction as a sustained and
controlled oral administration platform, exhibiting increased administration of NAP
under simulated colon conditions [104]. Drug model, characterization technique,
drug release %, time, and pH values of few CN/starch-based delivery carriers are
displayed in Table 6.
2.7 CN-Incorporated Pectin-Based Nanocomposite
The most complex polysaccharide found in plant cell walls, according to both physical and functional characteristics, is pectin. Plant growth, shape, development, and
defence are all impacted by pectin. Pectins are a class of polysaccharides that are rich
in galacturonic acid. They include homogalacturonan, rhamnogalacturonan I, and the
substituted galacturonans xylogalacturonan (XGA), rhamnogalacturonan II (RG-II),
and homogalacturonan (RG-I). Roughly 70% of pectin is constituted by galacturonic
acid, which is connected at the O-1 and O-4 positions in all pectic polysaccharides.
The poor gelling behaviour of pectin from other sources makes apple pomace and
orange peel dual primary originating sources of commercial pectin, even though
pectin is found in the cell walls of most plants. Pectin is a significant polysaccharide
that finds uses in food, medicine, and several other sectors. Its capacity to form gel
when exposed to low pH solutes or Ca
2+
ions is what makes it significant in the food
212 K. M. Sahu et al.
Fig. 7 Synthesis procedure of CMS@CS/(NAP@GQDs@Bio-MOF(Cu)). Reproduced with
permission from Elsevier [104]
industry.Pectin finds its application in the food business as jams, jellies, frozen foods,
and, more recently, low-calorie meals as a replacement for fat and/or sugar. It is also
used in edible films, as a paper alternative, in foams and plasticizers, among other
things. Since pectin is used in food industry, this is safe for humans and has biocompatible and biodegradable properties. Further, pectin is used in the pharmaceutical
sector to lower blood cholesterol and treat digestive issues [109, 110].
Aside from the abovediscussed applications, pectin has been tremendously implemented in the area of therapeutic delivery to make the carrier more viable in the said
application. Wang et al. designed the pectin-based oral colon-specific drug delivery
system (OCDDS) with improved and regulated delivery characteristics by accommodating 3-aminopropyltriethoxysilane-modified nano-carbon spheres (MNCS) into
2+
the pectin-Ca
OCDD surpassed that of pectin-Ca
the OCDDSs underwent a transformation where –COOH and –NH
tioned to –COOH
behaviour proportionate to the presence of –NH
COOH and –NH
film. The encapsulation efficiency of all nanocomposite films in the
2+
-based OCDDS. When introduced into the SGF,
groups transi-
+
and –NH
2
groups dissociate into –COO−and –NH
2
+
. This conversion contributes to an increased swelling
3
+
. In the SSIF environment, the –
3
+
, respectively, indicating
3
2
a shift in their chemical states. The electrostatic interaction played a crucial function
in impeding the resolution of the composite films. The transformation of –NH
occurred when the simulated environmentwas altered to a pH of 7.4, mirroring
–NH
2
+
3
the behaviour of OCDDSs in the SGF. As the reaction occurs at SGF, the dissociation reactions occur in SSIF and SCF conditions. Figure 8 depicts the fabrication and
disassociation mechanisms of composite films under distinct pH conditions. They
to
Tabl e 5 CN-incorporated HA nanocomposite-based drug delivery vehicles
Sl. No CN/HA-based drug delivery
Drug model Characterization Stimuli responsiveness Drug release References
vehicle
1 CQD-FA-HA Epirubicin UV–Vis, FTIR, XRD,
HRTEM, XPS, EDX, FESEM
2 HA-CD@p-CBA-DOX DOX UV–Vis, FTIR,1HNMR,
TEM, Zeta potential, CLSM
3 GO–CMC2–FI–HA/DOX FTIR, TEM, Zeta potential,
Confocal microscopic
4 GO–HA/DOX DOX TEM, AFM, FTIR, XRD,
Raman spectra, UV–Vis,
5 EPI-SWCNTs-DSPE-HA Epirubicin1H NMR, UV–Vis, FTIR,
Fluorescence spectra, Raman
spectra, TGA, SEM
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 213
pH Time (h) %
pH 5.5 72 86 [92]
7.4 42
pH 5.5 24 Over 50 [93]
6.8 –
7.4 Less than 20
pH 5.8 12 46 [94]
7.4 96 12
pH 5.2 65 26 [95]
6.3 10.9
7.4 ∼6.8
pH 5.5 12 60 [96]
7.4 48 20
Tabl e 6 CN-incorporated starch nanocomposite-based drug delivery vehicles
Sl.NoCN/Starch-based drug delivery
vehicle
1 CMS@CS/
(NAP@GQDs@Bio-MOF(Cu))
2 Starch/MWCNT-Gl Zolpidem FTIR, TEM,
3 PVA/Starch/GCN Silver-Titania TEM, XRD,
4 Starch–GNS Hydroxycamptothecin UV–Vis, FTIR,
5 Perlite/starch/SWCNTs-glucose CUR FTIR, XRD,
Drug model Characterization Stimuli
Naproxen FTIR, XRD,
BET, PL, SEM,
AFM
XRD, FESEM,
TGA,UV–Vis,
DLS
FTIR
SEM, TEM,
AFM, Raman
spectra, CLSM,
Fluorescence
spectra
FESEM, TEM,
TGA, DLS, BET
responsiveness
pH 1.2 2 16.04 [104]
pH 7.4 210 complete release [105]
pH Wat er,
pH 2.2 8 15 [107]
pH 4.5 24 Drug
Drug release References
pH Time
(h)
6.8 2 71.58
7.4 4 –
– – [106]
normal
saline and
simulated
wound
fluid
4.6 –
7.4 3
7.5
%
[108]
release
is more
at 7.5
214 K. M. Sahu et al.