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Carbon Nano-onions for Drug Delivery

Sora Yasri and Viroj Wiwanitkit
Abstract A variety of nanomaterials can be employed for medication delivery.
Encapsulating medications within nanoparticles, which can then be given to specific places in the body, is a popular strategy. Because of their small size, nanoparticles can travel more efficiently through the body and can also be tailored to release the therapeutic payload in a controlled manner. Some nanomaterials can also respond to external stimuli such as temperature or pH changes, triggering medication release at specific sites. These are only a handful of the numerous applications for medicine delivery that nanoparticles have. A nice illustration are carbon nano-onions. Carbon nano-onions are a special sort of carbon nanomaterial with an onion-like structure. They have medical applications, particularly in drug delivery. Carbon nano-onions’ small size and the unique structure allows them to be easily taken up by cells, making them an ideal vehicle for delivering medications to specific sites in the body. They are also easily modifiable in order to attach certain molecules, allowing for targeted distribution to specific cells or regions. Furthermore, carbon nano-onions haveshown promise as an imaging and diagnostic tool. They can be used to improve contrast in medical imaging, allowing for better diagnosis and treatment. Overall, carbon nano­onions have the potential to transform medicine and medication delivery by opening up new avenues for targeted and effective therapies for a wide range of diseases and ailments. The authors explore and describe the use of nano-onions for medication delivery. Also examples of applications for the treatment of cancer and infections are provided.
S. Yasri KM Center, Bangkok, Thailand
V. Wi w a n i t k i t ( Chandigarh University, Punjab, India e-mail: wviroj@yahoo.com
Dr. D. Y. Patil Medical College, Hospital and Research Centre, D. Y. Patil Vidyapeeth, Pune, India
Department of Eastern Medicine, Government College University Faisalabad, Faisalabad, Pakistan
Hainan Medical University, Haikou, China
Faculty of Medicine, University of Nis, Niš,Serbia
Joseph Ayobalola University, Ikeji-Arakeji, Nigeria
B
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385
386 S. Yasri and V. Wiwanitkit
Keywords Carbon nano-onions · Structure–property correlations · Synthesis · Therapeutic agents · Drug delivery
Abbreviations
CVD1Carbon vapour deposition DNA Deoxyribonucleic acid FDA Food and Drug Administration LbL Layer-by-layer

1 Introduction

Everyone experiences the sickness as a common condition. Essentially, cellular or organ level dysfunction is what causes the sickness. Medicine’s job is to control and manage the undesirable effects of the disease, which might include unintended morbidity and mortality. In terms of diseases, the two key medical processes are diagnosis and treatment. There are many therapeutic techniques avail­able, including medication, vaccines, radio management, and surgical interven­tion. However, employing “drugs” to manage disease is the approach that is most frequently used in medicine. Drugs are typically administered with the intention of treating a medical condition. These fundamental conditions must be met for a successful treatment outcome to occur: an efficient drug, a safe drug, a sufficient drug, good drug administration, good drug transportation in the body, and good drug distribution to the intended target. When treating any condition, medicine distribu­tion is a crucial issue. In contemporary pharmacotherapy, medication distribution has become a key concern. Today’s pharmacotherapy for the treatment of any disease starts with the fundamental question of how to have an effective drug delivery system to the focused target site. New drug delivery methods have been created with the advent of pharmacobiotechnology and may hold promise for pharmacotherapy. The utilization of nanotechnology is one of the unique technologies that make for an interesting illustration.
Focusing on the use of nanotechnology for drug delivery, the newly developed nano-object is usually used for attachment to drug that is called nanoconjugation. The conjugation of the nano-object is the basic application in designing of a new drug delivery system. Jain et al. noted that this technique was an important too in pharmaceutical and biotechnological research and could be applied for drug delivery systems for further use in various therapeutic purposes [1, 2]. At present, there are many conjugation applications (Table 13.1). Nowadays nano-objects are avail­able and applicable for drug delivery in clinical medicine. The use of nanocarriers
Carbon Nano-onions for Drug Delivery 387
can be the big advent for present management of medical disorders. The applica­tion of nanocarriers is presently used for management of the difficult- to-manage and complex disorders such as malignant tumors [3]. There are many reports on successful use of medial nanocarriers in medical oncology. Nevertheless, there are also applications of novel nanocarriers in other group of disease.
Fundamentally, nanotechnology is the application of extremely “small” items that are too small to be seen with the human eye (at the nanoscale). The nano-object is very small and has a variety of intriguing biological and physical characteris­tics. When compared to its twin at the supra-nanoscale, an object in the nanoscale has new electrostatic and biological properties. The main characteristics of nano­objects are the new ones, and technologists employ them for a variety of applications because of this. The current new emerging medical science that has only recently been launched in the field of medicine is known as nanomedicine. Medical biotech­nology is particularly intrigued by the use of nanotechnology in drug delivery. The program is currently being used in medical diabetology to control diabetes mellitus, the most prevalent metabolic condition in the world. In clinical medicine, insulin therapy for diabetes mellitus patients is frequently troublesome, and this widespread issue contributes to subpar disease control and unintended illness consequences. Medical researchers have been looking for an effective method of delivering insulin for a very long time. An effective example of the use of new pharmacotechnology is the administration of insulin using nanocarrier technology. According to Khafagy et al., the latest technology in clinical medicine today for managing patients with diabetes mellitus effectively is called the nanoacarrier [4].
Focusing on the application of nanotechnology for drug delivery, the term “nanoconjugation” refers to the process of attaching a freshly created nano-object to a drug. In order to build a new drug delivery system, the conjugation of nano­objects is the fundamental application. According to Jain et al. [1], this technique was significant for both pharmaceutical and biotechnological research and might be used to create drug delivery systems to implement in a range of therapeutic applica­tions. Because of their unique qualities, including high surface area, high reactivity,
Table 13.1 The various ways in which a nanomaterial can be used for drug delivery
Examples Details
Drug carriers
Targeted drug delivery
Controlled release
Imaging Some nanoparticles can be used for imaging purposes because they are fluorescent
Pharmaceuticals can be enclosed in liposomes, dendrimers, or solid lipid nanoparticles to prevent them from degrading and to increase their solubility and bioavailability
Nanoparticles can be functionalized with ligands that bind to specific receptors on target cells, allowing drugs to be delivered to the targeted location selectively
Drug efficacy can be increased and potential adverse effects decreased by using nanoparticles that release the medication under regulated conditions
or have magnetic properties that make it possible to see how drugs are delivered to the body
388 S. Yasri and V. Wiwanitkit
and programmability, nanomaterials are well suited for a wide range of biological applications, including drug administration [510]. There are numerous applications available right now. There are currently a wide variety of innovative nano-objects that can be used for clinical medicine drug administration. The current management of medical problems may benefit greatly from the usage of nanocarriers. Nanocarriers are currently being employed to treat difficult-to-manage and complex illnesses such as malignant tumors [3]. Many studies on the successful use of medial nanocarriers in medical oncology exist. Nonetheless, new nanocarriers have applications in various disease groups.
As previously stated, a number of nanomaterials can be used for medicine delivery. One prominent technique is to encapsulate drugs into nanoparticles, which may subsequently be delivered to particular locations in the body. Nanoparticles can travel more efficiently through the body due to their small size and can also be modified to release the therapeutic payload in a regulated manner. Furthermore, nanomaterials can be functionalized with specific targeting ligands, allowing nanoparticles to bind to and transport cargo directly to cells of interest. Some nanomaterials can also respond to external stimuli like temperature or pH changes, causing medication to be released at precise locations in the body. These are only a few of the many applications for nanoparticles in drug delivery. Nano-onions made of carbon are a good example. A unique type of carbon nanomaterial with an onion-like structure is known as carbon nano-onions. They have usages in medicine, particularly in the delivery of drugs. Because of their tiny size and distinctive structure, carbon nano-onions are an excellent method for delivering drugs to certain locations in the body. They can also be easily altered to attach particular molecules, enabling selective distribution to particular cells or locations. Additionally, carbon nano-onions have demonstrated promise as a diagnostic and imaging tool. In order to enable improved diagnosis and treatment, they can be utilized to enhance contrast in medical imaging. Overall, carbon nano-onions have the potential to alter medicine and medication delivery by allowing for more targeted and effective therapy for a wide range of diseases and maladies. In this work, the authors investigate and describe the usage of nano-onions for drug administration.

2 Carbon Nano-Onion: A Multi-Layered Nanocarrier

Any substance having at least one dimension smaller than 100 nm is referred to as a nanomaterial. Carbon atoms are arranged in various ways to create structures with special physical, chemical, and mechanical properties. These materials are called carbon-based nanomaterials [1116] (Table 13.2). Nanomaterials made of carbon, such as fullerenes, graphene, and carbon nanotubes, are some examples of carbon­based nanomaterials. Due to their special nanoscale features, they have a wide range of applications in industries like electronics, energy, and medicine. In nanomedicine and nano delivery systems, relatively new but quickly developing fields, materials in the nanoscale range are employed as diagnostic tools or to administer medicinal
Carbon Nano-onions for Drug Delivery 389
substances to specific targeted regions in a controlled manner. Nanotechnology offers many benefits in the treatment of chronic human diseases by delivering precise drugs to designated areas and targets. Recent years have witnessed a variety of impor­tant applications for the use of nanomedicine, including chemotherapeutic drugs, biological agents and immunotherapeutic agents in the treatment of various diseases [5].
Nanotechnology has transformed the field of pharmacology by enabling the devel­opment of more targeted and efficient medications. Nanoparticles with varied char­acteristics can be created to improve drug solubility, bioavailability, and stability. By encapsulating pharmaceuticals in nanocarriers like as liposomes, dendrimers, and polymeric nanoparticles, nanomaterials can also be employed to increase medica­tion delivery. These carriers can preserve drugs from degradation and increase their circulation time in the body, allowing for more precise medication targeting and a reduction in side effects. Furthermore, nanotechnology can be utilized to develop smart medication delivery systems that react to certain stimuli, such as pH or temper­ature changes, to release the drug at the targeted spot. This is especially helpful for treating cancer because focused release can increase efficacy while lowering toxi­city. We are only beginning to scratch the surface of what is possible with this fascinating technology, but nanotechnology holds enormous potential for advancing drug research and development [510].
The development of nanomaterial-based drugs has the potential to transform the area of medicine by permitting the creation of new types of therapy. Nanoparticles can be tailored to target specific cells or tissues in the body, increasing therapeutic efficacy while decreasing side effects. Furthermore, nanoparticles can be utilized to carry medications to the brain, which is challenging to accomplish using typical drug delivery methods. Overall, the use of nanomaterials in medication development has the potential to improve patient outcomes while also leading to the creation of novel
Table 13.2 Some forms of common carbon nanomaterials
Examples Details
Graphene Rolls of graphene sheets that can be single-walled or multi-walled
Carbon nanotubes
Fullerenes Carbon atoms grouped in a cage-like shape form spherical or ellipsoidal
Carbon nanofibers
Graphene oxide Graphene contains functional groups including oxygen, making it more
Diamond-like carbon
Amorphous carbon
Graphene sheets that have been rolled up and can be single-walled or multi-walled
molecules
Fibers comprised of carbon nanotubes or graphene sheets t hat have been aligned
hydrophilic and easier to digest
A non-crystalline type of carbon with characteristics similar to diamond but lacking the regular lattice structure
A type of carbon that is chaotic and lacks long-range organization
390 S. Yasri and V. Wiwanitkit
medicines. The modern form of therapy is currently crucial, especially when there is a mismatch between a drug’s dose or concentration and its therapeutic effects or harmful effects. Drugs can be attached to specially made carriers to achieve cell­specific targeting [5, 6]. Numerous nanostructures, including magnetic nanoparti­cles, polymers, dendrimers, silicon or carbon materials, and liposomes, have been investigated as drug delivery system carriers (Table 13.3).
Nano-onions are nanomaterials made up of nested spherical shells or “onions” constructed of various materials. Carbon nano-onions are the important class of carbon-based nanomaterials. They are composed of carbon atoms stacked in many layers to form a spherical or onion-like shape (Fig. 13.1). These layers can be composed of graphene or carbon nanotubes, which are both carbon-based nano­materials. Because of their structure, they have unique qualities such as increased stability, optical properties, and magnetic capabilities. A nano-onion’s center is often comprised of a magnetic or metallic material like iron or gold, while the outer shell is made of a semiconductor material like silicon or zinc oxide. Typically, the shells are only a few nanometers thick. Overall, nano-onions’ unusual structure makes them an intriguing contender for a variety of applications in sectors such as health, electronics, and energy storage. Nano-onions, as previously stated, are a sort of nano­material. They are made up of a series of concentric layers of graphene or carbon nanotubes. They are typically 3–5 nm in size, making them incredibly tiny and ideal for a wide range of applications. With this property, in pharmacology, loading of the drug to different layers is possible (Fig. 13.2). Nano-onions do not occur naturally in nature and are mainly created in the laboratory using various synthetic processes. As was mentioned earlier, the nano-onions are carbonaceous nanostructures made up of several fullerene concentric shells. Along with graphene and its derivatives, these cage-within-cage structures continue to be among the most intriguing and exciting carbon forms because of their distinct chemical and physical characteristics. They are a desirable option in many different fields, including biological systems, thanks to their superior biocompatibility and bio-safety. Upon surface functionalization, this nanomaterial exhibits minimal toxicity, high dispersity in aqueous solutions,
Table 13.3 Examples of nanomaterials that can be used for drug delivery
Examples Details
Liposomes These spherical vesicles are made of phospholipid bilayers and can hold both
Polymeric nanoparticles
Dendrimers These artificial polymer structures have many branches and resemble trees.
Metal nanoparticles
hydrophilic and hydrophobic medicines. Because they are biodegradable and biocompatible, they are a safe and effective medication delivery alternative
These are biodegradable polymer particles that can contain medications and release them over time. Because they may be designed to bind to specific cells or tissues, they are frequently utilized for targeted medication delivery
As they have several surface groups that can be functionalized with medicines or targeting molecules and can be employed for drug delivery
These are metal oxide, gold, silver, or other metal-based particles. They could be employed for medicine delivery
Carbon Nano-onions for Drug Delivery 391
and good medicinal efficacy. Despite the fact that carbon nano-onions and carbon nanotubes were practically discovered at the same time, their promise in medicinal applications still seems to be untapped.
Fig. 13.1 The drawing of basic structural models of carbon nano-onions
Fig. 13.2 Drugs loaded to
different layers of nano-onions
392 S. Yasri and V. Wiwanitkit
Describing the structural features of nano-onions, these are a distinct type of nanoparticles with a shell-like layering. They typically consist of a core nanoparticle encased in a number of concentric carbon shells. The size, surface area, electrical charge, and bonding of nano-onions all have an impact on their physical character­istics. Nano-onions are extremely reactive due to their small size, which also gives them a vast surface area. They can be employed in a range of applications, including medication delivery, catalysis, and sensing, thanks to their reactivity. Nano-onions have distinct electrical properties due to their layered structure. The numerous layers work as a single unit, acting as a series of capacitors capable of storing and releasing electrical charge. This feature makes them ideal for energy storage systems like batteries and supercapacitors. Nano-onions’ layered structure allows for efficient energy storage, making them potential materials for advanced energy storage appli­cations. Nano-onions are a very adaptable and helpful material in a variety of science and engineering sectors due to their unique physical characteristics. Conclusively, carbon nano-onions are identified by the concentric layers of graphene nanoparticles that resemble an onion. Generally, there are three different kinds of carbon nano­onions as presented in Table 13.4. Based on their size and the quantity of graphitic shells they have, the three different forms of carbon nano-onions can be divided into groups. The single-layer carbon nano-onion, which contains just one graphitic shell, is the smallest variety. The double-layer carbon nano-onion, which contains two graphitic shells, is the next size up. The multi-layer carbon nano-onion, which contains three or more shells, is the largest form. Unfortunately, the three various form of carbon nano-onions cannot be distinguished by the human eye. Without the use of specialist tools like electron microscopes or other equivalent techniques, these materials are too small to be seen. There are various reasons why it is crucial to classify the different kinds of carbon nano-onions. First, the physical, chemical, and mechanical properties of the carbon nano-onions can be influenced by their size and structure. A carbon nano-onion’s strength and stability, for instance, can be affected by the number of graphitic shell layers present, making it more or less suited for particular purposes. Second, it’s critical to comprehend the various kinds of carbon nano-onions and their characteristics in order to create novel applications for these materials. The unique characteristics of carbon nano-onions, such as their large surface area, make them potentially helpful in industries including nanoelectronics, catalysis, and biomedicine. Finally, categorization of carbon nano-onions facilitates comparisons across various investigations and helps standardize these materials. This may help us comprehend the characteristics and potential uses of carbon nano­onions. Because of their unique characteristics and biocompatibility, nano-onions have showed promise for a variety of biological applications [1722].
Nano-onions’ unique properties are significant for their application since they make them very adaptable and suited for a wide range of applications. Nano-onions are notable for their small size, high surface area, and unusual electrical and optical capabilities. These qualities make nano-onions excellent for use as sensors, cata­lysts, drug delivery vehicles, and other applications in electronics, photonics, and biomedicine. Furthermore, the ease with which nano-onions may be manufactured and manipulated increases their potential for usage in a variety of applications.
Carbon Nano-onions for Drug Delivery 393
Table 13.4 Three types of nano-onions
Types Details
Type 1 With a dimension that ranges from 2 to 5 nm, these are the smallest of the three
categories. They are utilized in many different applications, including medicine delivery, energy storage, and catalysis, and have a large surface area
Type 2 These have a diameter between 5 and 10 nm, making them slightly bigger than Type 1
particles. They are employed in products like lubricants and polymer composites and have higher number of graphene layers
Type 3 With a diameter ranging from 10 to 20 nm, these are the largest of the three categories.
They are employed in many different applications, including water purification and electrochemical sensors, and have a distinctive morphology with a curved surface
Table 13.5 contains a few examples. It can demonstrate that nano-onions have a variety of potential uses, such as sensing, drug administration, imaging, tissue engi­neering, and as therapeutic agents [22, 23]. Nano-onions are still relativelyyoung and understudied in comparison to other carbon nanomaterials such as carbon nanotubes and graphene. However,a recent study has demonstrated that they offer several advan­tages over other carbon nanostructures in biomedicine. Their distinctive shape, for example, enables for more effective drug delivery, and they can also be functional­ized with biomolecules for targeted therapeutic uses (Fig. 13.3). Overall, while there is still much to learn about the potential of nano-onions in biomedicine, they do show promise as a versatile and useful material for a range of applications.
Nanostructures with a wide range of applications and adaptability, they are used in a variety of technological and biomedical domains. It can highlight the poten­tial benefits of carbon nano-onions for biomedical applications such as bioimaging and sensing, among others. Because of their high biocompatibility, they offer ideal substrates for the creation of innovative healthcare devices [19]. The particular char­acteristics of nano-onions make pharmacology an attractive field for their use. Due to their layered structure, which enables high loading capacities and regulated drug
Table 13.5 Examples of biomedical applications of nano-onions
Examples Details
Drug delivery To work as a targeted drug delivery system, nano-onions can be functionalized
Imaging Nano-onions are advantageous for imaging applications due to their luminous
Tissue engineering
Biosensors Nano-onions can be utilized to detect biomolecules in biosensors. The material’s
with medicinal molecules, peptides, or antibodies. Nano-onions’ multi-layered structure can shield medication molecules from deterioration and release them in a regulated way
characteristics. They can be used to identify cancer cells or as fluorescent markers for biomolecules
Nano-onions can serve as tissue engineering scaffolds. Cells can grow and differentiate in a permeable environment thanks to the multilayered structure
high surface area and conductivity make it an attractive candidate for sensing platforms
394 S. Yasri and V. Wiwanitkit
Fig. 13.3 Brief concept for clinical application for nano-onion particles based therapy
release, they can be employed as drug delivery systems. The enhanced cellular absorption and targeted distribution to particular cells or tissues made possible by their diminutive size. Due to their optical and magnetic characteristics, nano­onions can also be utilized in imaging and sensing applications. The potential uses of nano-onions in pharmacology are constantly growing as a result of ongoing research.
Regarding using of a nanomaterial in pharmacology, the use of nanocarriers for targeted drug delivery is a new topic that tries to address some of the shortcomings of free drug administration, such as premature drug degradation, non-specific toxi­city, lack of tissue penetration, unwanted side effects, and multi-drug resistance. In this aspect, the nanocarrier technique has proven beneficial, with certain instances of Food and Drug Administration (FDA)-approved nanocarrier systems on the market [18]. To the best of our knowledge, the FDA has not yet approved nano-onions for any pharmaceutical purposes. While intriguing research on the potential applica­tions of nano-onions in biomedicine exists, further research is required to completely understand their safety and efficacy in people. It is crucial to understand that each new drug or medical device must go through extensive research and clinical studies before being approved for use in people by the FDA. Because the FDA approval procedure ensures the safety and efficacy of new pharmaceuticals and medical treat­ments, the approval is strictly required. There is always a danger connected with any new pharmacological application that does not have FDA approval. As a result, before beginning any new drug or treatment, it is critical to consult with a certified healthcare expert.
The topic of nanotoxicity should be discussed. A developing worry in the realm of nanotechnology is nano-toxicity. It is crucial to take into account any potential effects that nanoparticles may have on the environment and human health as they are used in a variety of applications. Regarding the common question on nano-onions, depending on their size, shape, and composition, they may be harmful. According to several studies, some varieties of nanomaterials might be hazardous to cells and other species. For the nano-onions, there are limited data. A recent study in zebrafish model showed that the nano-onions induced no toxicity [24]. On the other hand, in a different study, Xu et al. first hypothesized that reactive oxygen species may play a role in the ability of multiwall carbon nano-onions to cause deoxyribonucleic acid (DNA) damage and death in human umbilical vein endothelial cells [25]. In a related work, Ding et al. investigated the phenotypic responses of human skin fibroblast cell populations exposed to multiwall carbon nano-onions and multiwall