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Carbon Nano-onions for Drug Delivery 395
carbon nanotubes using whole genome expression array analysis and high content
image analysis. Ding et al. showed that multiwall carbon nanotubes and nano-onions
cause cell cycle arrest and enhance apoptosis/necrosis when cells are exposed to
them at lethal concentrations [26]. To completely comprehend the potential hazards
linked to these particles, more study is necessary.
As with any new technology, the possible environmental impact of nano-onions
must be considered. While there i s currently minimal evidence on the possible environmental implications of nano-onions, some studies indicate that they may have a
negative impact on environmental health, particularly if not properly disposed of. To
prevent potential environmental pollution from nano-onions, suitable safety precautions must be taken throughout manufacture, usage, and disposal. Using suitable
safety measures while handling, such as gloves and masks, can help to minimize
exposure to nanoparticles and lower the potential of contamination. To prevent the
release of nano-onions into the environment, adequate waste disposal and recycling
methods should be in place. To reduce the environmental impact of nano-onions,
researchers, manufacturers, and consumers must collaborate to guarantee that they
are manufactured and used in a safe and sustainable manner. However, while the
focus on the environmental impacts of nano-onions is raised, it should note that
there are also some reports that the materials are useful for pollution management
[27–29].
3 Synthesis of Carbon Nano-Onions
In the early 1990s, nano-onions, also known as onion-like carbon particles, were
discovered. They have been discovered to have numerous potential uses in domains
such as materials science, electronics, and biomedical engineering. Clinical research
on the medical applications of nano-onions is still underway and relatively fresh.
However, research has revealed that these particles have the potential to be used in
medicine delivery, cancer treatment, and imaging technologies. While nano-onions
have been studied for several decades, their prospective uses in clinical treatment are
currently being investigated and developed. Before they can be employed in a variety
of applications like biomedical imaging, drug delivery, and catalysis, nano-onions
normally need to be manufactured in a laboratory setting. It can be difficult to generate
nano-onions with uniform size and composition due to their complicated structure,
which is necessary for their controlled use in these applications. Additionally, the
synthesis procedure may have an effect on the stability and reactivity of the nanoonions. However, depending on the exact application, the nano-onions can be used
in a variety of ways once they have been created (Fig. 13.4).
In general, the synthesis process for nanomaterials involves shaping atoms or
molecules into tiny particles. This process might vary based on the exact type of material being produced, though. Nanomaterials can be created using a variety of methods,
such as chemical synthesis, physical synthesis, and biological synthesis. Creating
nested layers of materials using a combination of chemical and physical techniques
396 S. Yasri and V. Wiwanitkit
Fig. 13.4 Brief pathway from carbon molecule to carbon nano-onion
is typically how nano-onions are synthesized [30–32]. One popular process is “layerby-layer (LbL)” assembly, which involves depositing alternate layers of materials
that are both positively and negatively charged onto a substrate. Layers of the desired
materials are then removed from the substrate.
In essence, LbL assembly, commonly referred to as assembly techniques, is a
method for creating nanomaterials. A multilayer structure is created by the process
of layering layers of materials on a substrate. The components can be organic, inorganic, or a combination of organic and inorganic parts. A layer of one material
is first deposited on the substrate, and then a second layer of another material is
deposited on top of it. Up until the necessary number of layers has been reached,
this process is repeated. The substrate is submerged in a solution containing the
material to be deposited during each deposition phase. A charge- or pH-modulating
agent may also be present in the solution, which aids in controlling the deposition
process. The adaptability of LbL assembly is one of its advantages. It can be utilized
to make materials with a variety of characteristics, ranging from super hydrophobic
to super hydrophilic. It is also a reasonably easy and low-cost procedure that requires
only basic laboratory equipment. However, there are significant drawbacks to LbL
assembly. It takes time and requires a high level of precision. Furthermore, the resultant materials may be brittle, and the technique may not be suited for large-scale
production [33–37]. A nano-onion structure can be produced by repeatedly repeating
this technique, which will result in numerous nested layers. Nano-onions can also
be created using additional techniques like electrodeposition and sol–gel synthesis.
In order to create particles with the ideal characteristics for certain applications, the
synthesis process for nano-onions can be intricate and involves careful control of the
particle size, shape, and composition.
3.1 Annealing Method
Annealing is a heat treatment procedure that can be utilized in nanomaterial production. It entails heating the material at a high degree and then carefully cooling it to
minimize flaws and improve the material’s qualities. Annealing is not often a type
of LbL assembly, in which a material is built up LbL. Annealing, on the other hand,
can be used in conjunction with other synthesis processes, such as layer-by-layer
assembly, to produce nanomaterials with specific properties. Carbon nano-onions
can be created using the annealing technique [38, 39]. The following steps make
Carbon Nano-onions for Drug Delivery 397
up the general procedure. The manufacture of the carbon precursor substance, such
as fullerenes, carbon black, or carbon nanotubes, is the initial stage. The annealing
process is the next phase. Following that, the precursor material is heated to a high
temperature (often between 600 and 1000 °C) in an inert environment, such as argon
or nitrogen. The precursor material goes through a structural change during the
annealing procedure, which causes the production of carbon nano-onions. Characterization is the subsequent phase. Following fabrication, the carbon nano-onions are
examined using a variety of methods, including X-ray diffraction, scanning electron
microscopy, Raman spectroscopy, and transmission electron microscopy. Depending
on the particular precursor substance and the desired qualities of the carbon nanoonions, the specifics of the annealing procedure may change [40]. Overall, because
of its efficiency and simplicity, the annealing procedure has promise for the synthesis
of carbon nano-onions. Last but not least, the anneal approach can be used to synthesize nanomolecules by combining nano-onions with other molecules, such as boron
[41].
3.2 Carbon Ion Implantation Method
High-energy carbon ions are directed at a substrate material during the carbon implantation process, which results in the carbon penetrating the material and creating a
thin coating of carbon there. This process is used to create nanomaterials. Since the
technique does not involve adding layers to a material, carbon implantation is not
normally a type of layer-by-layer assembly. Instead, it is a modification process that
adds carbon ions to a substance to change its properties [42]. However, LbL assembly
and other synthesis techniques, like as carbon implantation, can be combined to
produce nanomaterials with particular features. Carbon nano-onions can be synthesized using the carbon ion implantation process. The following steps are included
in the procedure. The first step is to prepare the target material, which is typically
made of graphite. After then, the target material is attacked with high-energy carbon
ions. An ion beam accelerator is used for this. Carbon atoms in graphite undergo
structural modifications as a result of the high-energy carbon ions penetrating the
target substance. Carbon nano-onions are formed when the carbon atoms in graphite
rearrange themselves into an onion-like pattern. Following that, the freshly generated carbon nano-onions are retrieved from the target material using various extraction procedures such as sonication or centrifugation. Overall, employing carbon ion
implantation to produce carbon nano-onions is a successful procedure.
3.3 Arc Discharge Method
The synthesis of nanomaterials uses the arc discharge process. It involves vaporizing
and condensing a substance into nanoparticles using an electric arc discharge. This
398 S. Yasri and V. Wiwanitkit
process is frequently used to make fullerenes and carbon nanotubes [43–45]. It is not a
type of assembly done layer by layer. A different technique is LbL assembly, which
involves alternately adsorbing positively and negatively charged elements onto a
substrate to produce thin, multilayer films. Carbon nano-onions can be created using
the arc discharge process. This is the full procedure. Graphite rods should be used as
electrodes in a chamber that is filled with an inert gas, such as helium or argon. The
two graphite rods then form an electric arc, creating a high-pressure and temperature
environment inside the chamber. The outcome is that the graphite rods begin to
evaporate and create clusters of carbon vapor. The fast cooling and condensation
that follows causes these clusters to split into carbon nano-onions. By adjusting the
arc current, duration, and gas pressure, the size and characteristics of the carbon
nano-onions can be changed.
3.4 Carbon Vapour Deposition Method
Nanomaterials are created via a method called carbon vapour deposition (CVD1).
This process involves introducing a carbon-containing vapor into a chamber of a hightemperature reactor, where it reacts and deposits onto a substrate to create a thin film
or a nanomaterial. A sort of LbL construction is not CVD
of carbon atoms onto a substrate is a more direct way of producing nanomaterials.
However, by modifying the deposition conditions and adding additional chemical
precursors, several CVD
The CVD
process can be utilized to create nano-onions. Here’s a step-by-step guide
1
variations can be used to build layered structures [46, 47].
1
to synthesis. First, prepare the substrate by cleaning it with an appropriate solvent and
completely drying it. Place the substrate in the CVD
to the required level. The carbon precursor gas (such as acetylene or methane) is then
introduced into the reactor. Raise the temperature of the substrate and the precursor
gas to the desired level (about 700–800 °C). Carbon atoms from the precursor gas
will deposit onto the substrate after heating, generating minuscule carbon nanodots.
Continue the deposition process for the necessary time to build numerous layers of
carbon nanodots, which will eventually grow into a bigger structure known as nanoonions. The substrate should then be cooled before being taken out of the CVD
reactor. This is merely a brief summary of the CVD1procedure for producing nanoonions. It’s crucial to keep in mind that certain requirements and parameters may
change based on the intended dimensions, forms, and characteristics of the nanoonions. Last but not least, using the anneal method; nano-onions can be combined
with other molecules like Whey protein fibrils to create nanomolecules [48].
. The controlled deposition
1
reactor and vacuum the chamber
1
1
Carbon Nano-onions for Drug Delivery 399
3.5 Pyrolysis Method
The technique of pyrolysis, which involves thermal degradation, is used to create
several kinds of nanomaterials. In order to create nanomaterials, it involves heating
precursor materials to high temperatures without oxygen [49]. Additionally, pyrolysis
is not a LbL building method. The pyrolysis procedure can be used to create carbon
nano-onions. Under high temperatures and in the absence of oxygen, a carbon-based
precursor material, such as carbon black, graphite, or other carbon-rich materials, is
decomposed. The precursor material’s carbon atoms reorganize to create concentric
onion-like layers that make up the nano-onions. Pyrolysis is a popular method for
producing nano-onions. The following are step-by-step instructions for the process:
It must first begin with a pyrolysis-compatible precursor material. Carbon-based
compounds such as graphene and carbon nanotubes are popular. The precursor material is then heated to high temperatures in the presence of an inert gas, such as argon.
The substance is broken down into little particles, which can then reassemble into
onion-like formations. The resulting nano-onions can be purified further with procedures such as centrifugation or filtration. This method is currently being employed
in several studies to apply nano-onions for environmentally friendly purposes, such
as removing undesirable components from waste water [29].
4 Structure–property Relationships of Carbon
Nano-Onions
Nanomaterial structure–property correlations describe how the distinctive size and
form of nanomaterials affect their physical and chemical properties. The underlying
premise of nanoscience is that materials act differently at the nanoscale than they
do at larger dimensions [50–52]. Quantum mechanics becomes more significant in
determining material behavior at this scale. As a result, the properties of a nanomaterial may change significantly from those of the same material at a larger size.
A combination of quantum theory and physical theory can describe the behavior
and properties of nanostructures. Quantum mechanics describes particle behavior
at the atomic and subatomic levels, whereas physical theory investigates particle
interactions with their surroundings. The atomic and molecular structure of a material influences its qualities such as strength, conductivity, and optical properties in
nanostructures. Quantum mechanics explains how a material’s electrical and atomic
structure impacts its physical qualities. For example, a material’s electrical structure
can influence its conductivity or optical qualities, but its atomic structure can influence its mechanical properties. Physical theory explains how external influences such
as temperature, pressure, and electromagnetic fields affect the properties of nanostructures. When a material is exposed to a magnetic field or subjected to extreme
pressure, its properties can alter. We can explain how the structure of nanostructures
influences their qualities and how external factors can influence these attributes by
400 S. Yasri and V. Wiwanitkit
combining these two hypotheses. This comprehension is critical in the creation of
novel materials and technologies with enhanced characteristics and performance.
The intriguing properties of carbon nano-onions are the result of their distinctive
structural characteristics. The dimensions and quantity of layers of a carbon nanoonion greatly influence its characteristics. The surface area and pore volume of the
nano-onion grow together with the layer count, resulting in higher adsorption and
catalytic activity. The great thermal and mechanical resilience of carbon nano-onions
makes them intriguing materials for a variety of applications. Hence, carbon nanoonions are a fascinating field of research since their distinctive structure is a key
factor in defining their features.
The structure–property correlations of nano-onions are significant because they
enable us to comprehend how the size, shape, and composition of these particles affect
their physical and chemical properties. Using this knowledge, new materials with
specialized qualities can be designed and engineered for use in a variety of industries,
including electronics, energy, and biomedicine. Nano-onions can be used in a variety
of processes, such as catalysis, where their high surface area to volume ratio and
distinctive electronic characteristics can improve the activity and selectivity of the
reaction. Another instance is drug delivery, where the tiny size and biocompatibility
of nano-onions can allow for the effective and targeted administration of medicinal
substances to particular cells or tissues. Researchers employ a range of methods
including transmission electron microscopy, X-ray diffraction, and spectroscopy to
comprehend the structure–property correlations of nano-onions. These techniques
provide them the chance to look into the atomic and molecular makeup of the particles
and how that makeup impacts their characteristics.
In the fields of pharmacology and therapeutics, carbon nano-onions’ structure–
property interactions are important. The structurally distinct characteristics of the
nanomaterials, such as their high surface area, porosity, and biocompatibility, make
them desirable for use in a variety of therapeutic applications [53]. The efficacy of
drug delivery, biodistribution, and therapeutic efficacy of carbon nano-onions can
be improved by adjusting their size, shape, and surface chemistry. One such is the
employment of carbon nano-onions as medication delivery systems for the treatment
of cancer. Due to their high surface area and compact size, carbon nano-onions have
a high drug loading capacity and can cross biological barriers like the blood–brain
barrier. Additionally, the precise surface chemistry of carbon nano-onions can be
modified to enhance drug targeting to particular cells or tissues and to increase drug
release kinetics. Carbon nano-onions used as contrast agents in diagnostic imaging
are another illustration. Carbon nano-onions have a large surface area and special
electrical characteristics that make it possible for them to interact with magnetic
fields and produce contrast in magnetic resonance imaging. As a result, imaging for
illness diagnosis and monitoring may be more sensitive and more precise. Overall,
establishing new therapeutic applications for various diseases and conditions depends
on knowing the structure–property correlations of carbon nano-onions by adjusting
the characteristics.
Carbon Nano-onions for Drug Delivery 401
5 Modification of Carbon Nano-Onion-Based Nanocarriers
Nanocarriers are small vehicles that carry medications, genes, or other therapeutic
substances to specific cells or tissues in the body. They are often constructed of
biocompatible materials like polymers, lipids, or metals and can be programmed
to release their contents in a regulated manner. The significance of nanocarriers
stems from their capacity to increase medicinal efficacy and safety by enhancing
solubility, bioavailability, and targeting. Nanocarriers have numerous potential uses
in clinical medicine and pharmacology. Because they can improve the effectiveness and safety of medication delivery, nanocarriers have grown in significance in
pharmacology. Drugs can be made more bioavailable, stable, and soluble by being
enclosed in nanocarriers, which can enhance therapeutic results and lessen negative
effects. Additionally, nanocarriers have the ability to target particular cells or tissues,
which is helpful for treating conditions like cancer where focused drug delivery is
essential. Overall, using nanocarriers to enhance drug delivery and advance pharmacology is a promising strategy. They can be used to deliver medications to specific
cells or tissues in the body, which reduces side effects while enhancing therapeutic
efficacy [54–56]. Additionally, they can be applied in gene therapy to deliver therapeutic genes that address hereditary diseases. Nanocarriers can also be employed
for imaging, diagnostics, and the creation of novel medication delivery systems.
The surface chemistry of carbon nano-onion-based nanocarriers can be modified to
improve their capacity to encapsulate and distribute medications or other therapeutic
substances to specific cells in the body. Various chemical or physical techniques,
such as functionalization, conjugation, or coating with other materials, can be used to
achieve this. The objective is to enhance the biocompatibility, stability, and targeting
effectiveness of the nanocarrier for the targeted therapeutic applications. A nanocarrier must meet the fundamental requirements of being stable and biocompatible, as
well as being small enough to enter cells and target particular tissues or organs. Due
to their small size and distinctive shape, carbon nano-onions may be employed as
nanocarriers, depending on the specific application. Since virgin carbon nano-onions
are hydrophobic, as are the majority of carbon nanomaterials, they have low water
solubility. Without changing the sp
functionalization can be used to change the dispersibility qualities. The consideration of medication release at the target site is also necessary when using carbon
nano-onions in nanomedicine. Covalent bonds are insufficient for this goal; hence
non-covalent interactions are highlighted as a potential solution f or targeted release
[17]. The procedure of modification becomes crucial to achieving the application
in pharmacology. In some circumstances, adjustments may be required to improve
the material’s capabilities as a good nanocarrier. These alterations could involve
adding targeting molecules to the nano-onion’s surface to increase their specificity
or changing their surface charge to increase their stability and duration of circulation
in the body. Carbon nano-onions can be altered in a number of ways to improve their
characteristics or functionality. A few instances are presented in Table 13.6.
2
nanomaterial’s inherent features, non-covalent
402 S. Yasri and V. Wiwanitkit
Table 13.6 Several ways though which carbon nano-onions can be modified to enhance their
properties or functionality
Modification
method
Doping Doping carbon nano-onions with other substances, such as nitrogen or
Surface
functionalization
Coating Carbon nano-onions can be coated with other materials like polymers or
Size reduction Carbon nano-onions can be decreased in size even further to generate
Hybridization Carbon nano-onions can be combined with other nanomaterials, such as
Details
boron, can alter their electrical characteristics and improve their
conductivity
To increase solubility, stability, or bioactivity, the surface of carbon
nano-onions can be functionalized with various organic or inorganic
compounds
metals to modify their surface characteristics or improve their activity as
catalysts
ultra-small nanostructures with unique characteristics and applications
graphene or metal nanoparticles, to generate composite materials with
improved characteristics or functions
6 Carbon Nano-Onions in Drug Delivery
The process of administering medication or therapeutic chemicals to a patient’s body
is known as drug delivery. Because of their special characteristics, such as small size,
high surface area to volume ratios, and capacity to contain pharmaceuticals inside
their structure, nanomaterials can be employed in drug delivery. Drug delivery can
use nanomaterials in a variety of methods, including encapsulating pharmaceuticals
within their structure, affixing drug molecules to their surfaces, or employing them
as carriers to deliver drugs to particular locations in the body. This enables more efficient and targeted drug administration, lowering the risk of side effects and boosting
therapeutic efficacy. Due to their special characteristics, carbon nano-onions have
a lot of potential for medication delivery. Carbon nano-onions are a good choice
for targeted medication delivery because they have a large surface area and may be
functionalized with various compounds. The danger of adverse reactions in the body
is also reduced by the low toxicity and biocompatibility of carbon nano-onions.
Carbon nano-onions are also more capable of loading pharmaceuticals t han other
nanomaterials and can release them under controlled conditions. In comparison to
other nanomaterials, carbon nano-onions may therefore be a better candidate for
medication delivery [18] (Fig. 13.5).
Although nano-onions have demonstrated potential as a medication delivery
mechanism, there are significant restrictions and difficulties to take into account.
Given that some specific particles are formed of heavy metals like gold or silver,
one of their possible drawbacks is their potential for toxicity. The particles’ size can
also be problematic since they might be too big to efficiently infiltrate some cells or
tissues. Finally, stability, shelf life, production costs, and scaling up nano-onions for
Carbon Nano-onions for Drug Delivery 403
Fig. 13.5 Steps from
preparation of nano-onions
to usage as drug delivery
system
wider use are all possible challenges. However, despite these difficulties, researchers
continue to investigate the potential of nano-onions as a medication delivery mechanism, and it is possible that future study will find a way to overcome these restrictions. In addition to liposomes and polymeric micelles, nano-onions can also be
used as nanoparticles and liposome-based drug delivery systems. Solid particles
known as nanoparticles, with sizes ranging from 1 to 100 nm, are frequently utilized
as medication carriers. Targeted drug delivery frequently makes use of liposomes,
which are spherical structures formed of phospholipid bilayers and can encapsulate
404 S. Yasri and V. Wiwanitkit
pharmaceuticals. Polymeric micelles are amphiphilic block copolymer-based selfassembled nanoparticles that may transport hydrophobic medicines and be employed
for targeted drug administration. Each of these types of nano-onions has its own
benefits and drawbacks as a drug delivery method, and is chosen according on the
particular needs of the medicine and the condition being addressed.
6.1 Delivery of Therapeutic Agents
Because of its unique structure and physicochemical features, carbon nano-onions
have a high potential for medicinal agent delivery. The idea is that nanoparticles can
be functionalized or loaded with therapeutic agents like medications or genes and then
delivered to specific cells or tissues in the body. The small size of nano-onions enables
for better drug targeting and penetration, while their high surface area and reactivity
allow for effective drug loading and release. There are various phases involved in
using carbon nano-onions for therapeutic agent delivery, including functionalization, drug loading, and delivery. The surface of the nano-onions is often modified to
increase their biocompatibility and stability. Physical adsorption, covalent bonding,
or encapsulation inside nanoparticles can all be used to load drugs. Delivery can take
place in a number of ways, including injection, inhalation, and oral delivery. Improved
drug targeting and release, less adverse effects, and the potential to deliver medications to previously inaccessible parts of the body are all advantages of employing
carbon nano-onions for therapeutic agent administration. The possibility for toxicity
and the need for additional study to properly understand the biological interactions
and safety of carbon nano-onions are two drawbacks and issues to be aware of, as
with any new technology. The goof example of the research using nano-onions for
therapeutic agent delivery is published by Mamidi et al. Mamidi et al. propose a new
class of pH-controlled polycaprolactone/mercaptophenyl methacrylate functionalized carbon nano-onions composite nanofibers with a prolonged drug release profile
created via Forcespinning®. The degree of colloidal stability and physisorption of the
nanoparticles within the matrix is revealed by Mamidi et al. Furthermore, the in-vitro
cell viability of human fibroblast cells was tested, and good viability was observed.
Nonetheless, drug-enhanced pH-responsive composite nanofibers may have benefits
in biomedical research [57].
6.2 Delivery of Targeting Agents
Pharmacological substances or biological molecules that are intended to bind specifically to particular cells, tissues, or organs in the body are known as targeting agents.
With less negative effects on tissues other than the target, this selective targeting can
increase the effectiveness and efficiency of medication delivery. Nano-onions can be