Carbon Nanotube Marvels: Unveiling Synthetic Methods and Pharmaceutical Frontiers in Targeted Delivery

Abstract

Carbon nanotubes (CNTs) exhibit extraordinary strength and also possess remarkable mechanical, electrical, optical, thermal, and chemical properties. In this article, CNT’s structure, synthesis, production types, properties with detail in their types, applications, and future were discussed. CNTs are used as a drug delivery system in several ailments with specific importance on tumors and accompanying diseases. These are helpful because of their permeability through cell membrane barriers, and their tumor-accumulating properties make it a targeted nano-carrier. Cancer being the second most common disease with the greatest mortality rate is the area of main focus. CNTs are also playing a chief role in the transdermal drug delivery system (TDDS). TDDS is an area of interest in medical science because it is patient-compliant and eliminates the first-pass effect. Applications of CNTs in many domains due to their robust structure and metallic/semiconducting properties make them one of the favorable materials in nanotechnology.

1. Introduction

Today, one of the most rapidly developing and stimulating domains of scientific research is focused on the recently recognized all-carbon molecule family: the fullerenes. By theoretical prognosis CNTs and tubular fullerenes, may have exceptional chemical and physical properties [1]. On the footing of their strong capillarity, mechanical robustness, molecular sieve properties, etc., they might be utilized for exceptional causes [2]. In nanoscale sciences, one of the most stimulating discoveries is CNTs [3]. These hollow graphite tubules have several to several tens nanometers diameters [4]. CNTs were discovered by Ilijma in 1991 and are future’s major substances [5].

Distinguished by their exceptional mechanical, electrical, and photonic properties, CNTs have created an elevated level of research concern [6]. The distinctive properties due to their nanoscale structure have given them immense preference in the areas stretching from condensed-matter physics to chemistry, and from both academia circles to industry [7]. They are helpful in an extensive diversity of applications in structural, electrical, mechanical, thermal, biomedical, electronics, optical, and other domains of engineering, science, and medicine. Tubular CNTs could be used in these different areas due to their extraordinary properties that make them possibly helpful [8]. The exceptional, precise, cylindrical structure of CNTs remains fascinating as an engrossing model system for essential scientific research with possible discrete favorable applications [9].

2. Types of carbon nanotubes

CNTs are near-ideal whiskers comprising of folded graphene layers with cylindrical hexagonal lattice structure. During development, dependent upon the environments in which nanotubes are produced, they gather either as ropes (bundles) comprising of singular rolls and termed single-walled carbon nanotubes (SWCNTs) or multi-walled co-axial rolls, which are called multi-walled carbon nanotubes (MWCNTs), wrapped in 2D triangular lattices [10] which contrast in the assembly of their graphene cylinders [11]. The diameter and length of MWCNTs vary a lot from those of SWCNTs and, certainly, their characteristics are also very dissimilar [12]. SWCNTs synthesis usually involves a nanoscale catalyst metal. In the chemical vapor deposition (CVD) of SWCNTs, the well-known efficient catalyst species are the elements cobalt, nickel and iron, by which great SWCNTs produce can be gained. However, silver, copper and gold have never been informed to yield SWCNTs [13]. MWCNTs do not require any catalyst for their development either by the carbon arc or laser-vaporization methods [14].

2.1 Difference between SWCNTs and MWCNTs

1. SWCNTs are composed of a single graphene layer whereas MWCNTs have multiple layers of graphene

2. Catalyst is necessary for production of SWCNTs while MWCNTs can be manufactured without the use of catalyst

3. Bulk production is challenging for SWCNTs while it is easy for MWCNTs

4. More changes occur during functionalization of SWCNTs while MWCNTs show a lesser number of changes, but is difficult to recover

5. MWCNTs, in comparison with SWCNTs showed high purity

6. SWCNTs accumulate less in the body while MWCNTs show more buildup

7. SWCNTs evaluation and characterization is much easier than MWCNTs

8. SWCNTs are easily twisted while MWCNTs are difficult to twist [15] as shown in Figure 1.

Figure 1.

(a–d) Describes the structure of single-walled carbon nanotube and (e–f) is showing structure of multi-walled carbon nanotube [16].

3. Structure

Carbon allotropes are CNTs and these are sheets of graphite (which are called graphene) with one-atom thickness. These are rolled up into flawless circular solids with diameter of series of nanometers. The length-to-diameter ratio surpasses 10,000 and outcome is nanostructure [17]. Depending on the diameter and chirality, scanning tunneling microscopy (STM) measurements established that nanotubes are either metallic or semiconducting [18]. CNTs are distinctive nanostructures that can be evaluated as a framework of one-dimensional (1D) quantum wire. They are flawless cylinders acquired from the honeycomb latticework, exhibiting a crystalline graphite’s single atomic layer, called a graphene sheet [19]. Quasi-one-dimensional systems are more precisely CNTs: the atoms are situated on the surface of the cylinder in three-dimensional (3D) space; while for example, polyacetylene does not form 1D chain. This is a salient comment as the Peierls variability is accountable for interchanging single and double bonds and unfolding a void of 1.4 eV there, in inefficacy in CNTs’ case [20].

Carbon allotropes, incorporate 1D CNTs and whole 2D sheets of graphene. These carry on to attract attention as favorable plans of action for exploring the lower dimensions physics of electronics. Current research has revealed that graphene’s multilayer electronic properties are magnificently sensitive with respect to orientation between sheets, and in the case of bilayer, display powerful electronic associations when near to angle of magic twist [21]. Graphene sheets may include one or more tubular sheets in nanotubes. Figure 2 displays that through sp2 hybridization, every carbon atom is entirely bonded to three adjacent carbon atoms forming a flawless shell. Thus, micro-crystals of graphene can be nanotubes and its deformation is represented in Figure 3 [24].

Figure 2.

(a) Representation of honeycomb assembly of a graphene sheet. SWCNTs can be made by bending the sheet along lattice vectors. The two base vectors a₁ and a₂ are displayed. Folding of the (8,0), (8,8), and (10,-2) vectors direct to (b) armchair, (c) zigzag, and (d) chiral tubes, respectively [22].

Figure 3.

Deformations of an armchair [5,5] cylinder. (a) Shows the ideal tube structure while (b) and (c) illustrate the impacts of uniform twist and bend on the assembly [23].

CNTs have length and diameter of 20 and 80–120 nm range respectively. Their structure is bamboo-like wherein the arc of the section is angled to the endpoint. The endpoints are free and closed encapsulated catalytic particles. Following the Fowler–Nordheim behavior, the emission’s current is 1.1 mA/cm at an area of about 4.5 V/mm as shown in Figure 4 [26].

Figure 4.

A sheet of graphene that can be rolled into a single-walled nanotube by slicing out the sheet down the dashed lines and rolling up the sheet along vector C. a₁ and a₂ are the vectors of the graphene lattice. The dash-dotted lines represent the central symmetry guidelines in the graphene sheet, (n,n) and (n,0) and, or, armchair directions and the zigzag respectively. Also displayed are (n,m) indices around (14,3) [25].

Their length is generally in micrometer while diameters vary from 0.4 to 2–3 nm. Conventionally, SWCNTs come simultaneously to shape a bunch. SWCNTs are organized hexagonally in a bunch for the formation of crystal-like structure [27]. The distinctive structures leading to remarkable SWCNTs properties are that they have mechanical strength greater than that of iron, with 14,001°C thermal stability in a vacuum, and lower density than that of aluminum [7]. The chiral structure of the nanotube relies on their robustness, with near-armchair and small-diameter nanotubes manifesting high-rise tensile strengths. This noticeable structural reliance is overall accepted by the intrinsic structure depending on inter-atomic tension, with its accumulation at structural flaws, certainly prevailing in genuine nanotubes. These discoveries emphasize the structures of nanotubes that should be augmented when trying to contrive the strongest substances [28].

4. Synthesis

In 1993, after 2 years of discovery of CNTs, Iijima and Ichihashi, and Bethunetal by use of catalysts made of metal in the arc-discharge technique synthesized SWCNTs. Smalley and co-workers synthesized bundles of lined-up SWCNTs with small-diameter distribution and this remarkable development was attained by laser-ablation method. Yacamanetal first used the chemical vapor decomposition (CVD) method for the catalytic growth of nanotubes [29]. Figure 5 displays the synthesis apparatus for CNTs. To synthesize nanotubes, an anode made of graphite is immersed into an open vessel of liquid nitrogen consisting of graphite cathode or short non-consumable copper. The electrodes are brought into contact with the strike of an arc. The nanotubes are developed in the arc-plasma region and settle at the base of the vessel. The bottom of the vessel is like the shape of a funnel and closed with a faucet which opens periodically and automatically to wash out the nanotubes and this is suitable for continuous operation. In this arrangement, the anodes are threaded into each other and constantly fed via a simple sliding electrical contact. Liquid nitrogen level is automatically maintained in the insulated container by a level sensor and fill type. This alignment permits a 100% duty cycle for nanotube synthesis.

Figure 5.

Representation of continuous manufacture of liquid-nitrogen reaction chamber for the synthesis of nanotubes [30].

CNTs synthesis by CVD in comparison to patterned catalyst bundles leads to nanotubes that are developed from particular places on surfaces. Van der Waals self-assembly and applied electrical fields can control growing directions of nanotubes. The patterned growing perspective is attainable with distinct catalytic nanoparticles and has a capability on enormous wafers for huge bundles of novel nanowires. In nanotechnology and nanoscience, controlled nanotube synthesis unfolds intriguing chances [22].

The technique for carbon preparation is the procedure as follows: Around 18 V DC potential is administered between 9 mm diameter graphite rod (cathode) and another (anode) of 6 mm which are concurrent to each other in a reaction vessel which is kept in an inert gas atmosphere [31]. Thermal CVD of acetylene at 950°C helps to synthesize perpendicularly lined-up CNTs with elevated density on a wide range of cobalt-deposited silicon oxide substrate [32].

5. Production methods

Many methods are there for the manufacture of nanotubes. The well-known methods for the production are laser vaporization, electric arc discharge, and CVD which are responsible for producing a large variety of CNTs, as explained in Figure 6. By techniques such as electrolysis by graphite electrodes immersed in molten ionic salts, heat treatment of polymer, diffusion flame synthesis, and ball milling of graphite, CNTs can be produced [34]. Arc-plasma growth method is the most typical technique, which demands a chamber that is water-cooled sealed with particular bellows or sliding seals for constantly-cooled electrodes, time-consuming purge cycles, and complex gas handling equipment [35]. For withdrawing nanotube products, the chamber is opened after every limited synthesis run. The synthesis through carbon-arc nanotube technique eradicates almost all of expensive and complex machinery that is connected to nanotube traditional growth methods. Thus, a direct current power supply, graphene electrodes, and an insulated bucket filled with liquid nitrogen are all that is needed. This reaction could be employed on an industrial level and can run in a constant fashion [30].

Figure 6.

Representation of different processes used for the production of CNTs: (a) electric-arc method (University of Montpelier, France). (b) Oven laser-vaporization apparatus (Rice University, Texas). (c) Electrolysis experimental system (Brighton, United Kingdom). (d) Arc-discharge and CNTs production and transport in the casing. (e) Arc-discharge technique. (f) Laser ablation process. (g) Solar furnace (Odeillo, France). (h) Solar experimental chamber (Odeillo, France) [33].

5.1 Arc-discharge method

The primary technique for the manufacturing of macroscopic-size of MWCNTs was arc-growth. To provide this atmosphere, vacuum equipment, and sealed reaction chambers are required. The arc-grown MWCNTs are said to be appropriately graphitized which is contrary to catalytic tubes. A general issue apart from the requirement of vacuum equipment is the low-pressure neutral gas atmosphere of conventional DC arc-growth that is required to defer the growth to withdraw product from growth chamber [36].

The electric-arc discharge created between two electrodes made up of graphite under an inert atmosphere of argon or helium is the concept of this procedure. During the procedure, the sublimation of carbon occurs due to the high temperature between the two rods. The water-cooled reaction chamber synthesis is done that is first emptied and later loaded with an inert gas atmosphere (argon or helium, 660 mbar). The electrodes used are two graphite rods: by translation mechanism, one rod can move while the other remains fixed. The mobile electrode basically is anode; it is brought near to cathode so that the distance remains as small as (<1 mm) so that a (100 A) current passes between the electrodes in order to create plasma between them. The reason behind the consumption of positive electrode and ultimate sublimation of carbon is that the average temperature in the interelectrode plasma region is very high (near 4000 K). The anode has to be constantly translated so that the consistent distance between the rods and arc is maintained. Both electrodes are water-cooled and usually, the cathode diameter is larger than that of the anode. The fluctuations of plasma could be controlled if the distance between the electrodes and voltage (30–35 V) is maintained [37].

5.2 Laser ablation method

Under an inert atmosphere, in this method, a portion of graphite is vaporized via irradiation. The obtained CNTs that are soot containing are chilled at the sides of a quartz tube [33]. Using a modified pulsed laser deposition (PLD) process, CNTs could be successfully synthesized. In this silicon substrates are collected directly laser ejected carbon species. In this process, a catalyst layer is required. With the heat treatment process, the morphology of catalyst clusters varies, successively changing the field emission properties and morphology of CNTs noticeably. Modified PLD method is a traditional laser ablation technique when compared has a higher production rate, better collection efficiency, and is simple [38].

The well-coordinated structure additionally permits us to develop lined-up conjoining nanowires by settling electrochemically an aligned layer of a suitable polymer over the discrete lined-up CNTs. This perspective is specifically intriguing, as it permits surface attributes of the lined-up CNTs to be adapted to come across certain needs for specific applications while lined-up arrangement can be to a greater extent, held on to. These CNTs are of pronounced importance for several practical applications [39].

5.3 Catalytic chemical vapor deposition method

To produce high-quality CNTs, CVD acts to be the best potential way [3]. A better technique than regular CVD method in recent times has been known that is catalytic chemical vapor deposition (CCVD) [40]. During the past two decades, CNTs have been comprehensively studied and to produce CNTs of various crystallographic configurations, CCVD method has been employed by researchers [41].

For the CVD growth of nanotubes, three kinds of six-C hydrocarbons were used. The structures of as-prepared carbon products were greatly affected by the types of hydrocarbons. Top standard SWCNTs can be gained with source of benzene as carbon, MWCNTs were approvingly obtained with cyclohexane, while many flakes of graphite with hexane and a little MWCNTs were formed [42]. During the CVD growth, MWCNTs self-assemble into lined-up structures. For the development, squared iron patterns over porous silicon substrates are utilized. On the substrate, systematically placed arrays of nanotube towers are developed. Nanotube towers show sharp-edged ends and corners without splitting apart nanotubes from the blocks. Alongside the direction vertical to the substrate surface, within each block, MWCNTs are well coordinated. The nanotube base-growth mode substrate is involved in the mechanism of self-orientation of nanotubes. To form a firm bundle, the outermost walls of the nanotubes interconnect with their neighbors by van der Waals forces, during CVD growth. This permits substrates to grow perpendicular and to self-orient nanotubes [43].

5.3.1 The CoMoCAT process

By surge of pure CO at a complete pressure that generally stretches over 1 to 10 atm at 700–950°C, and its reduction to CO₂ and C is the procedure through which SWCNTs are grown. A harmonious outcome between Mo and Co can be observed that is necessary for the catalyst execution. Catalyst is only efficacious when at the same time both metals are there with low Co: Mo on silica support. Individually, they are unselective (Co only) or inactive (Mo only) (Table 1) [44].

Property/Process	Laser Ablation Method	Arc-Discharge Method	Chemical Vapor Deposition Method
Availability of raw materials	Problematic	Problematic	Easily and abundantly available
Requirement of energy	High energy requirement	High energy requirement	Moderate energy requirement
Control of the process	Tough	Tough	Easy and can be automated
Design of the reactor	Challenging	Challenging	Easy and can originate as a large-scale process
Rate of production	Low production rate	Low production rate	High production rate (CoMoCAT, HiPco)
Product purity	High purity	High purity	High purity
Process yield	High-yielding process (80–85%)	Moderate yielding process (70%)	High-yielding process (95–99%)
Requirements after the treatment	Refining is required	Refining is required	No extensive refining is required
Nature of the process	Batch type process	Batch type process	Continuous process
Cost per unit	High cost	High cost	Low cost

Table 1.

Comparison of CNTs production methods [8].

6. Purification

A vital step in the usage of CNTs as industrial materials is purification [45]. The CNTs contain numerous impurities, including amorphous carbon (soot), metal catalysts, graphite sheets, and any other material that may affect their properties [46]. The CNTs produced by the process of CVD have 5–10% purity on average. Therefore, extensive purification is required before using them in different biomedical applications [47]. The purification of CNTs also disrupts their structures thus it should be considered while removing the impurities. Following are the methods by which impurities can be removed:

6.1 Acid treatment

It removes the metal catalyst by firstly, exposing the surface of the metal to sonication or oxidation and secondly, to acid and then solvated. Nitric acid affects only metal catalyst, therefore, is used for this purpose [48].

6.2 Acid refluxing

It is used to reduce the impurities such as metal catalyst and amorphous carbon. The sample of CNTs is refluxed with acids such as sulfuric acid, nitric acid, and hydrochloric acid (most effective) [47].

6.3 Surfactant based sonication

It is used to remove tangled impurities from coalesced tubes. Sodium dodecyl benzene sulfate is dispersed in an organic solvent like methanol or ethanol. Since time needed for the settling of sonicated nanotubes is long, ultrafiltration and then annealing are performed at 1273 K temperature for 4 hrs. in the incidence of nitrogen gas. Annealing is done to adjust the structure of CNTs [49].

6.4 Magnetic purification

The ferromagnetic particles from their graphite shells are mechanically separated in this method.

6.5 Size exclusion chromatography

Separation of metallic and semiconducting SWCNTs can be done via size exclusion chromatography of DNA-dispersed CNTs (DNA-SWCNTs), which have the maximum resolution length categorization [50].

7. Functionalization of CNTs

Raw CNTs have highly hydrophobic surfaces due to which, CNTs’ functionalization is performed. It is a procedure in which preferred functional groups can be attached to the edges of CNTs, creating functionalized CNTs (f-CNT). Functionalization can be done by the following methods:

7.1 Covalent (chemical bond formation)

Polymer chains covalently bind to CNTs resulting in strong bonds between the attached molecule and the nanotube. It can occur by oxidation in which oxidizing agents like concentrated nitric acid are used to form carboxyl groups at the imperfections on the walls, like 5-membered rings and at the ends of the tube [51]. Arylation by the use of diazonium salts, nitrene cycloaddition, or 1,3-dipolar cycloadditions can also be utilized for the formation of carboxyl groups [52]. Hydrophilic polymers like polyethylene glycol can also be attached to oxidized CNTs to yield CNT-polymer conjugates which are durable in biological environments. SWCNTs prepared by this method can be benefited from in vivo and in vitro uses. Conversely, the physical properties like Raman scattering and photoluminescence of CNTs are radically decreased due to the change in structure accompanying covalent bonding, and for this reason, it cannot be employed to functionalize the CNTs for imaging purposes or usage in photothermal ablation [53].

7.2 Noncovalent bonding

Ideally, these types of CNTs should show particular properties; the more they are similar, the better will be their efficacy in biological functions. According to the literature, it is normally a more commonly applied technique of drug delivery. Noncovalent functionalization, contrary to covalent bonding, can be done by covering CNTs with amphiphilic polymers or surfactant particles [54]. P-p bonding is another type of functionalization, which can be completed by the loading of pyrene particles on the exterior of the CNTs. This technique can also be used on the specific strands of deoxyribonucleic acid by advantage of the aromatic deoxyribonucleic acid base units. It was reported to be unstable since it is disrupted by nuclease enzymes, thus the biological uses are so far inadequate. Noncovalent bonding does not interrupt the p-e network where the intrinsic physical properties of CNTs are well-preserved, except for shortening of length, displaying great use for photothermal ablation and imaging [55].

CNTs can also be functionalized through esterification and amidation of the CNT-bound carboxylic acids. These reactions can be classified into two categories: the utilization of the CNT-bound carboxylic acids and a direct addition of functional groups on the graphite surface [56]. Haddon with his co-workers initially published the usage of the acidic groups for adding long alkyl chains to SWCNTs via carboxylate-ammonium salt ionic interactions or amide linkages. Sun along with his co-workers reported that carboxylic acids esterification can also be employed to solubilize and functionalize CNTs of any size. A benefit of esterification is that they can be easily defunctionalized by acid- or base-catalyzed hydrolysis, permitting the regaining of CNTs from the samples [57]. The functionalized CNTs in solution can be placed directly onto a surface for several microscopy analyses.

8. De-functionalization

Once the CNTs formulated, from the soluble samples they are not visible and they can be regained from the soluble samples by the process of defunctionalization. The categorization of the defunctionalized samples supplies further proof for the deduction that the soluble samples, before defunctionalization, contain a considerable amount of CNTs. There are principally two kinds of defunctionalization processes:

1. Chemical defunctionalization in solution; like using of anhydrous hydrazine for the defluorination of fluorinated CNTs

2. Thermal defunctionalization in the solid state [58].

9. Applications

As for their exceptional properties, CNTs can be studied as desirable candidates in various nanotechnological uses, such as (bio) sensors, molecular tanks, fillers in polymer matrixes, and many others. On the other hand, the insolubility and the difficulty of handling any diluents have forced great restrictions on the usage of CNTs. Certainly, as-produced CNTs are unsolvable in all aqueous solutions and organic solvents. They can be dissolved in some diluents by sonication; however, precipitation occurs instantly when this procedure is disturbed. Instead, it has been shown that CNTs can interact with different compounds. The development of supramolecular complexes permits an improved processing of CNTs toward the production of advanced nanodevices. Furthermore, CNTs can encounter chemical reactions that render them more solvable for their mixing into organic, inorganic, and natural systems [59]. CNTs are able to effectively remove photogenerated charges, and increase the stability and resilience of a perovskite solar cell [60].

At present, wholesale CNT powders are merged into varied marketable goods stretching from sporting goods, motorized parts, and rechargeable batteries to water filters and boat hulls. Developments in CNT production and purification methods are allowing the incorporation of CNTs in large-area coatings and thin-film electronics [61]. Alignment and patterns of CNTs are principally important for manufacturing functional devices like sensors, scanning probes, field emitters, and nanoelectronics [62].

9.1 CNTs in cancer

CNTs are used for drug delivery in many diseases with specific importance on cancer and related ailments (celiac disease, osteoporosis) because of their ability to penetrate through plasma membrane barrier and tumor-accumulating properties [63]. They enter into the cytoplasm via a “tiny nanoneedle” machination, which enables the delivery and transport of the load therapeutics or molecules into the aimed tissue [64]. CNTs are considered favorable candidates by reason of their needlelike structure, suitable biocompatibility concentrations, and great surface area that is conscientious for molecular cargo binding and extensive modification [65]. The structure of CNTs enables the insertion of drug within the tube and likewise permits the surface coat of the active ingredient on the tubes. Functionalization through polymers or conjugation of targeting moieties enables greater loading efficiency and drug attachment [66]. Adherence of the chemotherapeutic agents to the outer surface of the CNTs can be via either noncovalent or covalent linking [67].

Both MWCNTs and SWCNTs are used in drug transport system. Conventional management of cancer can have adverse effects on healthy tissues. Hence, CNTs-based drug transport systems must be developed to deliver chemotherapeutic drugs. CNTs are also useful for early identification of cancer cells. There are various distinctive protein biomarkers that are overexpressed in tumor cells, and they offer a lead-in for early identification, prediction, continuing observation succeeding curative surgery, examining treatment in progressive ailment, and forecasting therapeutic reaction [68]. They can also be used as injectables [69]. Chemotherapeutic drug molecules with very low penetrability across the blood-brain barrier pose a negative effect on brain cancer treatment [70]. Iverson et al. showed that CNTs enhance CpG oligodeoxynucleotide immunotherapy in glioma treatment. SWCNTs were functionalized with polyethylene glycol after that conjugation with CpG oligonucleotide leading to an augmentation of CpG uptake in both intracranial gliomas and in vivo. CpG accelerated toll-like receptor family (found intracellularly and distinguish carbohydrates, lipids, peptides, and nucleic acid structures, conveyed by microbes) in the glial cells to prevent tumor development in glioma models [71].

9.2 CNTs in ischemia

Use of CNTs for drug delivery can be of huge advantage for neuroprotection accomplishment in chronic neurological diseases including ischemic stroke [72]. SWCNTs functionalized with amine groups through amidation reaction increases the endurance of neurons to injury due to ischemia. Neurons are guarded from injury and their roles are also recovered with amine-modified SWCNTs without therapeutic involvement [73]. Al-Jamal with his colleagues also demonstrated the efficiency of amine-modified MWCNTs to treat ischemic stroke [74].

9.3 CNTs in neuroregeneration

Advances in nanotechnology for neurotrophin delivery systems are favorable concerning their capability to stimulate neurotrophin signaling for neuroregeneration and neuroprotection [75]. Neurotrophins are proteins participating in neuroprotection and are crucial for the functions and development of neurons and could be carried to the site of action by CNTs. The necessities for effective regenerative engineering include neuroplasticity (rejoining of circuits of neurons, afterward elevation of the plasticity of their tissues), neurorestoration (conservation of neurons), and neurogenesis (advancement of an atmosphere favorable to regrowth of the relapsed neurons). The strong knowledge of the nervous system and enhancement of curative methods for neurological involvement are thought to have a substantial influence on neuroscience investigation because of the innovations in nanomedicine [76].

9.4 Gastric emptying

CNTs can increase gastric emptying and enhance gastric function, and therefore escalate to some degree the activity of pepsin [77].

9.5 Cosmetics

CNTs are now utilized in cosmeceuticals predominantly for skin care. Analogous to fullerene, CNTs alone function as and are efficient as phytocompounds delivery systems in biomedical uses. A short time ago, a SWCNT was conjugated with curcumin for efficient delivery. Hyaluronic acids with CNTs were also studied recently, and additional clinical trials are desirable to evaluate their biosafety. Though, research on the uses of phytocompounds with CNTs in cosmeceuticals and skin care is still to be performed [78].

9.6 Transdermal drug delivery system (TDDS)

TDDS can be defined as a self-sufficient, distinct dosage form, also called a “patch” [79]. The major purpose of a TDDS is to carry drugs into blood via the skin at a fixed rate with least intra- and interpatient changes [80]. The superior characteristics of administration through skin are: controlled and sustained drug delivery, enhanced patient compliance and ease of application, option of local and systemic delivery, prevention of adverse systemic effects by reason of accumulating the drug at a local area, and avoidance of GI tract problems and hepatic first-pass metabolism. Drug delivery through skin is a challenging task: the stratum corneum appears as the leading obstacle of the skin for transdermal and dermal routes of administration for drug permeation, although it is only around 15 μm in thickness [81]. CNTs are spread outside the skin’s stratum corneum, and only the active drug is projected to penetrate the body obstacles [82]. Furthermore, a new transdermal patch means for transporting nicotine was developed and proved effective which was based on an active film of aligned CNTs (approximately 1.5e7 nm in diameter) crossing over a solid polymer layer [83]. A non-covalently functionalized SWCNT was shown to inhibit the progression of melanoma by transdermal drug delivery [84].

9.7 Implants

As a result of post-delivery pain, the body often rejects implants, while due to miniature size, nanohorns and nanotubes (both SWCNTs and MWCNTs) easily bind with supplementary amino acids and can be developed for inserting artificial joints exclusive of host rejection reaction. Furthermore, owing to their exceptional properties like extraordinary tensile strength, CNTs can work as implants and bone alternates if stuffed with calcium and molded in the form of bone [85].

9.8 Biodegradability and biocompatibility of CNTs

If nano-biomaterial disintegrates into the body, the cancer-causing and other forms of lethal effects may trigger adverse reactions. Additionally, non-biodegradable CNTs can gather in tissues and become harmful to health. Toxicity-related reports shown to examine the improved ways of degradation impacts of CNT-based drugs [86].

9.9 CNTs and antibacterial

The alarming worldwide increases in mortality and morbidity due to resistance of drugs that develop via natural selection are greatly connected to systemic infections related to multidrug-resistant (MDR) bacteria. Inpatients are at greater risk of hospital-acquired microbial infections. These are adapted versions of prevailing antibiotics that proved inefficient against MDR bacteria. CNTs can be more cost-efficient and effective than conventional antibiotic therapies. For instance, targeted transport of amphotericin B to cells by means of covalently functionalized CNTs is inexpensive than using traditional liposomal amphotericin B. This renders targeted delivery the desired choice for treating leishmanial infections [87].

9.10 Preservatives

CNTs can be used in preservatives because of their antioxidant property. They have already been utilized in antiaging creams to avoid their oxidation [88].

9.11 CNTs for platelet activation

Many research studies have documented the function of CNTs in activation of platelets. Research was led to describe the results of titanium dioxide rutile, diesel, and CNTs on platelet activation, and it was concluded that SWCNTs stimulated platelet activation, aggregation, and platelet granulocyte complex formation [89]. Moreover, CNTs have been reported to essentially stimulate the blood platelets, therefore they are known to cause arterial thrombosis [90].

10. Conclusion and future perspectives

There is a saying that good things come in small packages, nanotechnology has certainly materialized this saying. The CNT’s uses in the domain of energy storage and exchange, wastewater treatment, and environmental monitoring also designed for green technology are research regions from the point of view of future nanotechnology. Revolutionary developments in electrochemical devices are the integration of CNTs in the field of energy applications. New alternatives have opened regarding biotechnology as CNTs are capable of passing through membranes, carrying biomolecules, genes, and vaccines deep into the organs and target cells. CNTs are useful for artificial implants, tissue generation and repair of defective organs due to their property of being biodegradable. Improvements in purification, production, and chemical alteration of CNTs have enabled their integration into large-scale coatings and thin-film electronics. Within this tiny, mysterious world that exists within the CNTs are many more attractive hidden phenomena. However, much irrefutable evidence are accumulating on CNT’s tolerance and safety. Further, the social perception of CNTs is changing favorably. This provides an opportunity to check CNT’s administering into the circulatory system with persistence and impending advancements. The therapeutic concepts may be revolutionized in the future and give a ray of hope for a lot of incurable ailments treatments. The accelerated and organized innovations and imaginations are required to take nanotechnology to top and will also be helpful in different fields of science and technology. CNTs will offer a new material mechanism in drug delivery globally by providing a targeted approach toward clinical applications.

Conflict of interest

The authors declare no conflict of interest.