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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5362_Библиотеки_им_академика_М_И_Перельмана.pdf
Carbon-Based Nanomaterials for Drug Delivery: Past, Present, Future … 115
Tabl e 5 Applications of CNOs in biomedical field. Adapted and reproduced with permission from
MDPI [114]
Name of CNOs Application Comments
f-CNO reinforced zein
hydrogels
f-CNO-polycaprolactone Anticancer
p-CNO-glassy carbon
electrode
f-CNO-gelatin hydrogel Anticancer
Ox-CNO/Chitosan/Polyvinyl
alcohol
p-CNO, Ox-CNO,
Fluorescent CNO
Anticancer
drug
delivery
drug
delivery
DNA sensor Large surface area and fast electron transfer are
drug
delivery
Tissue
engineering
Cell
imaging
Exhibit pH-responsive sustained drug release
spanning over 15 days, Enhanced mechanical
strength, improved cytocompatibility
pH-dependent drug release, improved
biocompatibility, mechanical strength, and
hydrophobicity
the reasons behind sensing biomolecular
interaction
Sustained release of 5-FU drug over 15 days and
improved tensile strength indicating the prospect
in tissue engineering and drug delivery
Exhibit negative allergic response, tissue
regeneration capability
As an alternative to organic dyes, it can provide
high resolution cellular image, Exhibited
improved stability and cytocompatibility
3.6 Nanohorns in Drug Delivery
Although Carbon nanohorns (CNHs) were synthesized a decade back, their applications in biomedical field are coming up very recently [115]. CNHs are considered a
bridge between carbon nanotubes (CNT) and fullerenes. They are one-dimensional
2
carbon nanostructure consisting of sp
carbon atoms. Because of the presence of
conical shape front tip CNHs are also known as nanocone [116]. They are structurally very similar to CNTs, the only difference is they are end capped by a cone
or horn. The cone angle is about 120°, length 40–50 nm, and diameter is 2–5 nm
(Fig. 8)[117, 118]. CNHs are frequently found to be in aggregates in different shapes
and morphology, e.g., dahlia flower like, bud like, seed like, etc. Among them, the
most prominent is dahlia like spherical structure having a diameter of 80–100 nm
[119, 120]. CNHs havevery different and unique properties which are absent in other
nanostructures. Because of their special beneficial properties, they are employed in
nano-oncology for delivery of anticancer drugs [121, 122]. A detailed study of the
application of covalent modified and non-covalent modified CNHs in cancer therapy
is available in article [116].
CNHs are synthesized by vaporizing some carbon material without any added
metal catalyst followed by quenching for removal of impurities [123]. Primarily three
methods are employed, e.g., arc discharge, laser ablation, and joule heating. Because
of the absence of metal impurities, the toxicity level in CNHs is much lower than that
of CNTs. This is the biggest advantage of CNHs for their biomedical applications
[124–126]. In addition to t his, CNHs have large surface area and high porosity. The
116 N. B. Singh et al.
Fig. 8 a Morphological representation of A Carbon Nanohorns with dahlia like structure and B
single CNH. Reproduced with permission from Elsevier [117], b TEM image CNH showing dahlia
like features. Reproduced with permission from Elsevier [118]
asymmetric structural features allow them easy loading and releasing of drugs either
through tip or walls [127]. CNHs can undergo covalent and non-covalent functional-
ization depending on whether more stable interactions or less stable interactions are
formed due to the formation or disruption of chemical bonds during their synthesis
Fig. 9 [116]. Covalent interactions involve attachment of organic molecule such as
polymeric materials on the surface to enhance biocompatibility and tailored properties. Non-covalent functionalization on CNHs includes π–π stacking interactions,
electrostatic interactions, packing bioactive molecules inside cavity, adsorbing metal
nanoparticles over the outer surface, etc. CNHs are more reactive than CNTs since
there is a loss of aromaticity due to the presence of many defect sites. Thus they
are prone to easy chemical modification. A lot of researches have been performed
on the ability of CHNs role as drug carrier to the site of tumor in cancer treatment.
In most cases of drug delivery by CHNs cisplatin is used as a chemotherapeutic
agent [128]. The efficacy of CHNs in drug delivery is enhanced with their NIR
absorption ability which recognizes their role in photothermal and photodynamic
therapy [129]. The heat generated during NIR irradiation kills the cancer cells in
photothermal process. However, in photodynamic process, cell death happens due to
the singlet oxygen and other reactive oxygen species. People have also explored the
conjugate role of photothermal with drug vector. For example, doxorubicine (DOX)
and cis platin were loaded on the surface of CNHs through π–π stacking interactions
of non-covalent functionalization along with suitable photo and chemotherapeutic
protocols for treatment of various cancer cells(Fig. 10)[128]. CHNs are also reported
for their biosensing applications. A glucose biosensor is fabricated by encapsulating
glucose oxidase in the Nafion-CNH composite [130]. Polysodium styrene sulfonate
functionalized CNHs can adsorb myoglobin and can act as an effective biosensor for
the detection of H
[131]. A recent report investigated the simultaneous determi-
2O2
nation of dopamine, uric acid, and ascorbic acid using CNH modified glassy carbon
electrode [132].
Carbon-Based Nanomaterials for Drug Delivery: Past, Present, Future … 117
Fig. 9 Various routes of functionalization in CNHs. Adapted and modified with permission from
[116]
Fig. 10 Scheme for preparation of Cisplatin and Doxorubicin loaded SW-Carbon Nanohorns.
Reproduced from Ivyspring International open [128]
118 N. B. Singh et al.
3.7 Fullerene in Drug Delivery
Fullerenes are clusters of carbon represented by Cn(n > 20) with a spherical surface.
2
All carbon atoms are sp
hybridized and form pentagons and hexagons by covalent
bonding with each carbon atom on the surface. Fullerenes are associated with some
interesting physical and chemical properties beneficial for drug delivery. Research
findings reported that fullerenes are highly compatible with the biomolecules. Thus
fullerene is considered a promising carbon-based nanomaterial in biomedical field
[133–137]. However, toxicity and high drug loading are the key limitations of this
material for its full utility. Several strategies are applied to overcome these issues
such as stabilization and functionalization.
The delivery of drug docetaxel is studied using functionalized fullerene (C
60
Higher apoptosis rate and antitumor efficacy was observed in case of functionalized
fullerene-docetaxel than that of free drug [138]. Controlled drug release systems
using functionalized fullerene were prepared as nano-vesicles. Various drugs such as
cisplatin, 5-fluorouracil cyclophosphamide, etc., are carried by these nano-vesicles
for release in a controlled delayed manner [139]. In the research by Wang et al. the
solubility of fullerene is improved by reacting with surfactant CTAF with magnetic
property. It is further modified by introducing DNA to hold anticancer drug DOX
[140]. Then C
@CTAB/DNA system is coated with HA-SS-COOH for controlling
60
agglomeration and to improve the morphology. It has been observed that cleavage of
disulphide bonds of glutathione significantly reduced the extratumoral environment
and encouraged the delivery of drug at the specific site. Glycine functionalized C
is reported for delayed drug delivery. Misra et al. have investigated drug delivery
of glycinated C
-fullerene conjugated with N-desmethyl tamoxifen and observed
60
higher drug loading and drug retaining efficacy [141]. Similarly, cancer drug DOX
conjugated with fullerene using a thioketal linking group for controlled drug delivery
application. This system exhibits better therapeutic effect, less toxicity, and slowdrug
release property [142, 143]. Some significant applications of fullerene in recent drug
delivery systems are listed in Table 6 highlighting its promising future in this field.
).
60
4 Challenges and Future Perspective
As discussed in this chapter, it is clear that in the past few years, carbon-based
nanomaterials (CBNs) are creating a lot of interest in drug delivery and biomedical
field [16, 17]. CBNs are equipped with remarkable optical, mechanical, and chemical
properties. The unique properties at the nanoscale alter their behavior inside the
body. Despite the long list of advantages, the CBNs have a number of limitations.
Scaling up the synthesis of CBNs to the industrial scale is not up to the mark.
Most of the CBNs face serious challenges while large scale production [15]. A
thorough understanding is required to devicean optimum methodology to tackle these
issues. The synthesis methodology must be economical, environment friendly and
Carbon-Based Nanomaterials for Drug Delivery: Past, Present, Future … 119
Tabl e 6 Some recent drug delivery applications of Fullerene. Adapted and reproduced with
permission from MDPI [1]
Drug used Method Functionalization Research inference
Ibuprofen Conjugation Transition metal N4
Hydroxyurea Conjugation Pristine C60,BC59,SiC59,
Doxorubicin Complexation Tolu ene Drug delivery to
Doxorubicin Complexation Tolu ene Function as
Choloroquine Chemical bonding Pristine C60and
N-desmethyl
tamoxifen
Reaction with glycine N-desmethyl tamoxifen
clusters
AlC
,
59
chloroquine
and glycine
Delivery of
ibuprofen
Hetero-fullerene for
drug delivery
cancer cells
photosensitizer
Al and Si doped
fullerene as drug
delivery vehicle
Controlled drug
release
produce high yield. Moreover,the toxicity issue of CBNs is one of the most important
challenges that need special attention [25]. Generation of toxic by-products to cause
health and environmental issues need stringent regulatory protocols during synthesis
and commercialization of CBNs. The poor aqueous solubility is another limitation
of CBNs application in drug delivery. Utilization of high end surface engineering
technology, these CBNs can be made biocompatible along with water solubility
which is a highly desirable property in drug delivery and tissue engineering field
[43]. Long term fate of the CBNs needs careful assessment to bring them further for
clinical trials to treat serious ailments. Thus the compatibility, safety, and efficacy of
CBNs are of prime importance to work on for their promising future applications in
drug delivery and clinical field.
5 Conclusions
The present chapter highlights the different roles and functions of CBNs in drug
delivery and biomedical applications. Throughout history, drug delivery has evolved
from traditional formulations to sophisticated nanomaterial-based strategies, and
CBNs have emerged as promising candidates for revolutionizing this domain. By
examining the historical journey, current breakthroughs, and promising prospects,
this chapter paves the way for harnessing the power of carbon-based nanomaterials
to users in a new era of precision medicine and improved patient outcomes. Use of
a number of carbon nanomaterials in medical sector with their positive and negative
impacts have been discussed in this chapter.
120 N. B. Singh et al.
Acknowledgements The authors are thankful to the management of Sharda University for
providing facilities and resources to conduct the present study.
Conflict of Interest The author declared no potential conflicts of interest with respect to the
research, authorship, and publication of this article.
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