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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 … 215
Fig. 8 Fabrication and disassociation mechanisms of composite films under distinct pH conditions.
Reproduced with permission from Elsevier [111]
investigated the cumulative release profile of different samples and concluded that
the best sample showed a release rate of 32.17%, 22.%, and 63.89% in SGF, SSIF, and
SCF, respectively [111]. Hussien et al. developedan innovative versatile magnetic GO
nanocarrier that boasts innocuous characteristics, increased stability, and supreme
capabilities for both drug loading and release. The in vitro medication administration
capability of GO-Fe
and PEC-GO-Fe3O4was systematically examined to eval-
3O4
uate the impact of polyelectrolyte complex (PEC) conjugation on the administration
proficiency of GO-Fe
nanocarrier. The administration studies were performed
3O4
at pH 5.5 to simulate the endosomal pH of cancer cells and at pH 7.4 to imitate
the normal physiological environment. In acidic medium, the PEC-GO-Fe
3O4
-PAC
showed higher drug administration profile [112].
2.8 CN-Incorporated Guar Gum-Based Nanocomposite
A new agrochemical called GG is made from the endosperm of cluster beans. The
drought-tolerant plant Cyamopsis tetragonoloba, which is affiliated with the Leguminosae family, is the prime source of GG. GG is mostly composed of intricate
carbohydrate polymer of mannose and galactose, but in differing ratios. It is mostly
utilized as an ingredient in the food, pharmaceutical, paper, fabric, explosive, and
cosmetics industries in the form of powder. GG can be used in industry because of
216 K. M. Sahu et al.
its capacity to establish hydrogen bonds with molecules of water. As a result, its
primary uses are as stabilizer and for thickening. Additionally, it helps to manage a
number of health issues, including diabetes, colon cancer, heart disease, and bowel
motions [113].
GG’s combination with others improves its qualities and expands its uses in a
variety of sectors for a broad spectrum of purposes, including medicine delivery,
food, pharmaceutical, and cosmetics, and water purification. Derivatives of GG have
also been shown to be therapeutically significant in a few physiological illnesses
[114]. Moreover, CNs-based GG nanocomposite therapeutic carriers have shown
efficacious results in drug delivery. For instance a novel composite membrane, incorporating acrylic acid (AA) grafted GG and carboxy-functionalized MWCNT (fMWCNT), has been synthesized and thoroughly characterized for their application
in the sustained administration of diclofenac sodium. The interaction between the
matrix and filler, particularly at concentrations up to 1 wt% f-MWCNT, resulted in
a more refined dispersion of the filler, enhancing water persistence and therapeutic
retention properties. Concentrations greater than 1 wt% of CNs cause irregular filler
networking and lead to reduced water persistence and suboptimal therapeutic retention behaviours. Notably, the 1 wt% f-MWCNT level exhibited the slowest drug
release, whereas the fastest release was observed at 3 wt%. The release patterns
followed a non-Fickian mechanism. The reason behind the non-Fickian release of
drug was the impact of viscoelastic relaxation which was more pronounced in case of
composite based on 0.5 and 1 wt% compositions [115]. Another environmentfriendly
hydrophobic membrane was fabricated from composites of poly (diethylene glycol
dimethacrylate)-grafted carboxymethyl GG (CMG-g-PDEGDMA) and carboxy-fMWCNT via in situ method. The developed nanocomposite membrane was implemented for the transdermal administration of a hydrophobic therapeutic, namely
diclofenac sodium. Figure 9 demonstrated cumulative drug %, preparation route, and
SEM images of CMG-g-PDEGDMA with different concentrations of PDEGDMA.
The presence of f-MWCNT increased the hydrophobic nature of the membrane,
resisting rapid swelling compared to both pristine CMG and CMG-g-PDEGDMA
membranes. The optimal concentration of f-MWCNT led to an extremely slow
release, addressing concerns of drug overdose while simultaneously improving the
half-life period of the therapeutic molecules for long-term usage [116].
2.9 CN-Incorporated Agarose-Based Nanocomposite
Agarose (AG) is a linear polysaccharide that mostly constitutes of α-l,4-1inked 3,6-
anhydro-α-Lgalactose and β-1,3 linked D-galactose. It also includes a small number
of ionized sulphate groups. When AG is dissolved in water, it produces thermoreversible gels. Gelation takes place at temperatures below 40 °C, but melting
tends to occur at temperatures over 90 °C. AG is generally insoluble in organic
solvents and is unable to form gels. AG molecules become hydrated and dissociate
at temperatures greater than 90 °C [117]. The unique properties of AG, including its
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 217
Fig. 9 Cumulative drug %, preparation route, and SEM images of CMG-g-PDEGDMA. Reproduced with permission from Elsevier [116]
exceptional biocompatible behaviour, thermo-reversible gelation ability, and physiochemical traits, facilitate its application as a biomaterial for controlled and localized drug administration and cell development. In tissue engineering and reconstructive medicine, AG and its derivatives are commonly employed in biomedical
processes including neurogenesis, angiogenesis, spermatogenesis, cartilage creation,
bone regeneration, wound healing, and artificial pancreas. AG-based biomaterials
have, therefore, shown to be adaptable for some tissue engineering usages [118] and
more prominently for targeted drug delivery uses. AG demonstrates a neutral surface
alteration over a range of pH values. This property enables AG to transport therapeutics with little protein corona generation and improves delivery efficiency. Because
AG-based hydrogels crosslink readily through physical interactions, they have been
widely used as a drug administration system. It is feasible to regulate the diffusion of
different medications through different pathways by altering the AG concentration
and additive selection in AG-based gels due to their porous structure [119].
Owing to the above-mentioned point, researchers active in the field of therapeutic
delivery applications are interested in formulation of AG drug delivery vehicles
by accompanying AG with other polymers and nanomaterials specifically CNs. To
accomplish this objective, a pH responsive and biocompatible hydrogel comprising
CS, AG, and GO was engineered with glyoxal utilized as a cross-linker by Rajaei et al.
They carried out an investigationto introduce a potential method to achieve improved
drug loading efficiencyas well as sustainable administration of 5-fluorouracil (5-FU).
From the experimental data, the medication accommodating and entrapment proficiency percentages were calculated of about 57% and 92%, respectively. Notably,
a highly efficient and sustainable therapeutic administration profile was noticed at
pH 5.4, with nearly the whole 5-FU content administrated within 48 h. When breast
cancer cells were incubated with CS/AG/GO/5-FU, the recorded cell viability was
approximately 23%, underscoring its potent anti-cancer capability. These findings
suggest that the synthesized nanocarriers hold significant potential as pH-sensitive
218 K. M. Sahu et al.
nanocarriers for the regulated administration of 5-FU in the context of breast cancer
treatment [120]. Rajabzadeh-Khosroshahi et al. revealed that g-C
helped to enhance drug release from CS/AG/g-C
g-C
/Cur nanocomposites led to a significant reduction in cancer cell viability of
3N4
/Cur nanocarriers. The CS/AG/
3N4
3N4
nanosheets
up to 12% in contrast to free Cur. Furthermore, cells treated with the as-synthesized
nanocomposite exhibited a remarkable apoptosis rate of 8% in the breast cancer cell
line MCF-7, highlighting the great efficacyof the nanocomposites in inducing cancer
cell death. The therapeutic release studies showcased an outstanding and regulated
pH-sensitive administration profile for CS/AG/g-C
, carrying unique properties
3N4
for the delivery of CUR [121].
2.10 CN-Incorporated Carrageenan-Based Nanocomposite
Carrageenan is a collection of sulphated galactans that are obtained from various
red seaweeds belonging to the Gigartinaceae, Hypneaceae, Solieriaceae, Phyllophoraceae, and Furcellariaceae families. The seaweed species Chondrus crispus,
known as Carraigin in Ireland and Carrageen Moss in England, is the prime source of
Carrageenan. These galactans exhibit ester sulphate content varying from 15 to 40%
and alternately contain (1 → 3)-α-D- and (1 → 4)-β-D-glycosidic linkages [122].
The typical Mw of commercial CGs ranges from 100 to 1000 kDa. Carrageenan
is predominantly categorizes into several kinds, including λ, κ, ι, ε, and μ,allof
which incorporate 22–35% sulphate groups. Its solubility in potassium chloride led
to this categorization. The anionic sulphate groups on CGs have a pKa value of
around 2, which controls the amount of ionization in various fluids. Especially in
sauces and food items, carrageenans find extensive use in commercial applications
as stabilizing, thickening, and gelling agents. In addition to these uses, carrageenans
are employed in industrial applications, pharmaceutical formulations, cosmetics,
and experimental medicine. Carrageenan CGs’ biological and toxicological characteristics have demonstrated a number of possible medicinal qualities, including as
immunomodulatory, anticancer, antihyperlipidemic, and anticoagulant effects [123,
124]. Also its addition with CNs leads to make it a more efficient material for drug
administrative carrier under the influence of pH variation and near-infrared (NIR)
light.
NIR renowned for its non-harmful nature and deep tissue penetration capabilities emerges as an appealing stimulus for remotely regulated biological applications.
The literature on NIR-activated carriers for medication administration is currently
limited, with a predominant emphasis on systems incorporating gold nanostructures.
In a notable contribution, Estrada et al. engineered a light-responsive nanocomposite
hydrogel using κ-carrageenans and MWCNTs. NIR irradiation initiated the delivery
of a model drug, methylene blue, from the developed hydrogel. The MWCNTs served
as nanoheaters, effectivelyraising the temperature of the gel through the photothermal
alteration of the MWCNTs [125]. Utilizing the acylation method, Vinothini et al.
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 219
successfully synthesized κ-carrageenan grafted onto GO. Subsequently, the polymerized GO with κ-carrageenan was further modified through conjugation with biotin,
aiming to achievetarget specific drug administration. The fabrication process of GO/
κ-Car-biotin composite is illustrated in Fig. 10.
The resulting GO/κ-Car-biotin composite displayed remarkable accommodating
efficiency for DOX and displayed pH-sensitive therapeutic release. The chemical
modification of GO with κ-carrageenan was implemented to enhance the dispersion
properties of GO. This κ-Car-grafted GO was then conjugated with biotin through
Fig. 10 Schematic illustration of fabrication process of GO/κ-Car-biotin composite. Reproduced
with permission from Elsevier [126]
220 K. M. Sahu et al.
ionic interactions, creating a system that targets vitamin receptors for DOX delivery.
The medication administration analysis was conducted at three distinct pH levels
(2.8, 5.5, and 6.8). Under acidic conditions at pH 2.8, a substantial increment in the
therapeutic release rate, amounting to 74%, was observed. This heightened release
can be attributed to pH-dependent hydrophobic interactions between GO and DOX,
facilitated by their respective structural features. The disruption of H-bonding, π–π
stacking, and electrostatic interactions between DOXand GO nanosheets was readily
apparent in the acidic medium at pH 2.8 [126].
2.11 CN-Incorporated Glucomannan-Based Nanocomposite
Glucomannan (GM), a highly promising polysaccharide recently integrated into the
realm of drug delivery, is characterized by its hydrocolloidal nature and comprises
β-1,4 linked mannose and glucose residues. Belonging to the mannan family, GM is
ubiquitously allocated in nature, predominantly found in softwoods (as part of hemicellulose), roots, tubers, and various plant bulbs. Despite its diverse origins, konjac
GM, procured from the tubers of Amorphophallus konjac, is the most commonly
utilized type. Although inherently hydrophilic, GM’s water solubility may be diminished because of the creation of robust hydrogen bonds resulting from purification
or drying methods [127]. Because of its creation source, hydrophilic behaviour, and
other functionality, GM has diverse potentiality in biomedical applications.
GM combination with CNs incorporates some interesting features in drug administration process to achieve the desire outcomes. A straightforward marine bioinspired surface modification procedure was implemented to enhance the interfacial
adhesion of carboxyl-functionalized multiwalled carbon nanotubes (CCNT) with
the konjac glucomannan (KGM) matrix, facilitating the fabrication of aerogels.
By skilfully manipulating ingredient ratios, Wang et al. engineered aerogels with
well-organized pore structures and enduring features. The resulting KGM/PCCNT
aerogels showcased robust networks characterized by extensive hydrogen bonding
throughout their structure. The administration of 5-FU incorporated into the KGM/
PCCNT4 aerogel was approximately 48% at pH 1.2 and 62% at pH 6.8, respectively after 11 h [128]. One of the primary sources of glucomannan carbohydrate
is salep. The MWCNT/hydrogel nanocomposite was fabricated using conventional
radical polymerization, with the integration of salep as a natural carbohydrate source.
In the absence of MWCNT, the release of TCH from the hydrogel exhibited nonFickian transport. Conversely, with the inclusion of MWCNTs, the release demonstrated Fickian transport. Additionally, experiments were executed to examine the
administration of TCH under varying pH levels, pressures, and temperatures. These
parameters validated the efficacy of the hydrogel nanocomposite, based on salep
carbohydrate, in facilitating the release of TCH [129].
Carbon Nanomaterial-Incorporated Polysaccharide-Based … 221
3 Challenges and Future Prospective
Achievement of precise control over drug release rate and assurance of site-specific
targeted therapeutic delivery are the most crucial steps in the drug delivery applications. In addition to addressing toxicity concern with some specific CNs, ensurance of
the overall biocompatibility of the polysaccharide-based nanocomposite is necessary
for their clinical translation. Further, to ensure the high effective therapeutic delivery
and minimal side effects though the implementation of such materials in in vivo
applications is the prime objective of the research. Therefore, development of meticulous techniques which are suitable for the preparation and implementation of these
materials in laboratory as well as in real world applications is required. Also, future
research should explore innovative strategies for integrating diagnostic and therapeutic functionalities within a single nanocomposite platform, opening avenues for
personalized and precision medicine. Solving these challenges requires concerted
efforts from interdisciplinary teams. Continuous exploration of these perspectives
will drive the development of safe, effective, and clinically viable nanocomposites
for the future of drug delivery.
4 Concluding Remarks
The chapter underscores the significance of combining CNs with various polysaccharides which offers a spectrum of unique properties that can be strategically
harnessed for improving drug delivery. This amalgamation not only capitalizes on
the inherent advantages of both CNs and polysaccharides but also addresses challenges in drug delivery. These advanced smart drug administration systems are mainly
pH responsive which facilitate the release of drug molecules at the particular sites
to encourage target-specific sustainable release. Furthermore, CN/polysaccharidebased therapeutic delivery carriers help in improving bioavailability, increasing drug
loading sites and enhancing time period for prolonged drug release.
Acknowledgements The authors acknowledge UGC India for awarding SJSGC Doctoral Fellowship to Krishna Manjari Sahu.
Conflict of Interest The authors declare that there is no conflict of interest in publishing this
article.
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