The Application of Graphene in Drug Delivery

TABLE OF CONTENTS

ABSTRACT

1. INTRODUCTION

2. HISTORY

3. STRUCTURE OF GRAPHENE

4. PROPERTIES OF GRAPHENE
4.1. Micromechanical Cleavage
4.2. Liquid Phase Exfoliation
4.3. Chemical Vapour Deposition
4.4. Chemical Methods
4.5. Mechanical Properties
4.6. Electrical Properties

5. APPLICATIONS OF GRAPHENE FOR REAL-TIME APPLICATIONS
5.1. Flexible Graphene Transistors
5.2. Graphene Sensors
5.3. Graphene for lithiumesulfur (LieS) battery
5.4. Graphene displays
5.5. Structural Composites
5.6. Catalysts Support
5.7. Polymer Masterbatches
5.8. Functional Inks

6. Use of Graphene for COVID
6.1. Graphene-based anti-viral surfaces and coatings
6.2. Graphene-based electrochemical biosensors
6.3. Graphene-based Field-effect Transistor for Biosensing
6.4. Graphene-based Piezoelectric Biosensors
6.5. Graphene based on Gene-editing Technology (CRISPR/Cas)
6.6. Multilayer Graphene Nanofoams

7. CONCLUSION AND CHALLENGES

8. WAY FORWARD

REFERENCES

ACKNOWLEDGEMENT

I would like to express my heartfelt gratitude to my supervisor Dr.Soni Mishra for being a guiding light and encouraging me at each and every step.

I would also take the time to thank the Head of Department Dr. Vijay Kumar Gupta for giving us the opportunity and to entrust me.

At last, I would like to thank my family for being a great support.

ABSTRACT

Graphene, has the potential of being a revolution in the world, from extraordinary properties-electrical, chemical and mechanical. benzene like structure of the hexagonal components of the lattice quite useful properties in drug delivery

Discovered by Geim and Novoselev by the famous 'Scotch-tape method', graphene has been a matter of interest for the world of nanotechnology. With increasing popularity different methods for its industrial production are being devised - Hummer's method, micromechanical cleavage, liquid-phase exfoliation, ball milling,laser thinning of graphite crystals and anodic bonding.

Such as strength and flexibility explore its potential in nanocomposites.Presence of s and p electrons alone makes carbon based nanomaterials a deal of attraction. Graphene is a zero band-gap semiconductor with very high electrical conductivity.Chirality, ambipolar field effect, pseudospin, anomalous Quantum hall effect, high mobility of charge carriers and excellent thermal conductivity exhibited by graphene. On applications of graphene which are very vast, we focus on its use in drug delivery.

graphene has been used in antiviral surfaces and coatings for fatal SARS-COV 2. Graphene based materials xplod extensively for the antimicrobial potential.Efforts are being made to explore its antiviral potential against negative sense respiratory synctial virus (RSV). Multilayer Nano-foams have huge potential for development of variety of components needed to fight Covid-19.comic capability of effectively crossing biological barriers ,drug loading efficiency make it an effective candidate for continued research to aid drug delivery.

Keywords- Graphene,drug-delivery, Scotch-tape method, properties,SARS-COV 2,Respiratory syntial virus(RSV),COVID-19

1. INTRODUCTION

Graphene is a single atom, thick, nanosized, 2D structure. It provides a high area and adjustable surface chemistry to make hybrids.

In this review, Graphene in the context of its application in the drug delivery system will be analysed. Graphene was first isolated using mechanical exfoliation within the now famous ‘scotch-tape method’ . The benzene-like structure of the hexagonal components of the lattice allows it to be thought of like a giant aromatic poly-molecule . Even without further functionalisation, this structure provides useful properties in the delivery method: aromatic molecules may bind to graphene through non-covalent interactions between carbon-rings and the large relative surface area of 2D geometry permits a single graphene flake to be decorated with a raft of different aromatic groups

2. HISTORY

Graphene,a hexagonal structure, consisting of spA2 hybridised carbon atom[1].It is the building block of carbon nanotubes and graphite.Graphene was first discovered by Geim and Novolosev when they isolated and characterized pristine Graphene [2]by the famous 'scotch-tape method' essentially this simply entails using a piece of adhesive tape to remove flakes of graphite from a slab of highly ordered pyrolytic graphite (HOPG), which are deposited on a silica slide. This process is repeatedly done till we essentially come down to one atom thick layer graphite which is called graphene[3].

However, this was not the first time ultra thin carbon films had been observed a number of reports in the past where unilayer graphene was observed[4]. Graphite oxide was synthesized before in the late 1890s and 1950s by Staudemeir[5]and Hummers[6] respectively.There were also reports of Graphene oxides by 1962.[7].

But it wasn't until unique properties of graphene were discovered did ,the true picture emerge[2].

The author Geim and Novolosev were duly awarded the Nobel prize for Physics in 2010 for this ground­breaking work in the world of nanoparticles[8].

Post the discovery of such a high potential material, various developments took place. It was tried to manipulate in different ways to yield benefits from its unique properties.The industrial production also became a requirement as the 'Scotch-tape method' wasn't viable. Currently prevalent is the 'Hummers method', device by William Hummers in late 1950[4].The method entails using powerful oxidising agent and strong acids to strip apart the graphene layers from a source of graphite,the graphite oxide deduced, is to be further used to make graphene. Other graphene production methods exist, but aren't used in the mainstream- including Ion Implantation, Chemical Vapour Deposition [9][10] and Liquid Phase Exfoliation[11] and epitaxial growth upon a silicon carbide substrate[12].

3. STRUCTURE OF GRAPHENE

The electronic structure of graphene's basic unit is presented below (Fig. 1) for a far better understanding of the electronic properties of graphene and their derivatives.

Abbildung in dieser Leseprobe nicht enthalten

Fig. 1. (aec) Fundamental aspect of graphene bonding properties and (d) SEM image of single­layer graphene

It is interesting to notice that structural holes permit the phonons to go unobstructed, which results in a big thermal conductivity in graphene. However, this property has not been observed in graphene oxide and other derivatives of graphene due to the altered band structure [13, 14]. The classification of graphene as metal, non-metal or semimetal remains a matter of debate and requires further research [13]. But, thanks to the presence of metallic layers with very low bandgaps, it are often treated as a semimetal with an exceptional theoretical background [13, 14]. As a whole, it has numerous remarkable characteristics that are not observed for other non-metallic materials also as for the exiting ideal semimetals. The properties of graphene solely depend upon the amount of layers and therefore the defects present within the graphene layers. For example, the theoretical surface area of pristine graphene is ~2630 m2/g which is far above the area of lampblack (850e900 m2/g), carbon nanotubes (100e1000 m2/g), and many other analogues [13]. On the otherhand, the surface area of a fewlayers graphene, graphene oxide, and lots of other derivatives are much less in comparison to single-layer graphene [13]. Due to these exceptional properties, graphene acts as an ideal material for many modern technologies including electronic applications along with many other materials as substrate or template [13]

4. PROPERTIES OF GRAPHENE

Post,the simple 'Scotch-Tape method' and various other methods there have been numerous efforts to understand the unusual electronic structure that graphene possesses, and to obtain mono and few layer graphene using various physical and chemical approaches.The other techniques include micromechanical cleavage, liquid-phase exfoliation,ball milling, laser thinning of graphite crystals and anodic bonding[13]. Chemical routes such as microwave assisted exfoliation,ball milling,lazer thinning of bulk graphite crystals[14]. Chemical Deposition of carbonaceous precursors on transition metals and precipitation of carbon from the surface of SiC[15,16].

4.1. Micromechanical Cleavage

Ebbeson and Hiura observed the accidental folding and tearing of graphite sheets when it HOPG surface was scanned using an atomic force microscopy(AFM) tip[17].

These meshes were attached to the photo resist after baking,tape was used for sending a down to a single layer by dissolving the photo resistant acetone,the flakes are suspended. By dipping and washing in water and propanol, these flakes were transferred onto a solid substrate of SiO2(300nm/Si(n+doped. On further simplification method such as Raman Spectroscopy and AFM were devised.

Simplest and most efficient of all the methods currently available. The only major issue with this method was it unpractical to use it for industrial production.

4.2. Liquid Phase Exfoliation

Mono and few layer graphene is also obtained by this method and the scale of production can also be large. The produced graphene is further modified chemically and then made into thin films.[18, 19]

Graphene is produced by interaction between solvent and graphene layers.The energy required is supplied by ultrasonication,shear mixing and ball milling [20, 21].

Ultrasonication creates waves through liquid medium, which eventually creates microbubbles .These microbubbles grow and eventually collapse violently,reaching pressure up to 20 MPa and rapid heating/cooling at a rate upto 10[9] ksA-1 [22].

Graphene is exfoliated sheets are stabilized to avoid restacking. Commonly used surfactants like sodium dodecylbenzene sulphonate bring about stabilization by electrostatic means[18].

4.3. Chemical Vapour Deposition

Decomposition of a carbon precursor at high temperature on substrate is essentially CVD.The hydrocarbon gas acts as the source of carbon decomposes at the surface.Transistion metal substrates additionally lower the required energy by acting as a catalyst and determine the decomposition mechanism [23].

By this approach, high-quality graphene can be obtained.

4.4. Chemical Methods

Chemical methods are used majorly because of their high yield and high output. Methods like chemical oxidation and exfoliation like the Hummers method.

Although the process of oxidation enables easy exfoliation of GO,it causes intrinsic graphene to be lost.

To revert GO graphene reduction step is necessary.This RGO can be obtained by numerous reduction approaches like chemical, thermal,electrochemical photocatalysts, solvothermal and microwave[24,25]

The yield can further be enhanced by mechanical methods such as ball milling and ultrasonication [26].Alkali metal ion species can be introduced between layers of graphite, which when treated with ethanol results in High yields of few layer of graphene[27].

4.5. Mechanical Properties

Carbon atoms attached by a covalent bond of the maximum stress that a material can tolerate prior to fracture is associated to its defect-free lattice. Defects in lattice tend to reduce the tensile strength.

Suk et al. used AFM in contact mode combined with finite element method(FEM) modelling [28]. Monolayer GO was found to have Young's modulus of 207 GPa, when compared to pristine graphene. with graphene possessing such high mechanical strength and flexibility it becomes obligated to explore its potential as a reinforcement material in nanocompisites[29].

The presence of s and p electrons alone makes carbon based nanomaterials a deal of attraction. Abundance of carbon,less energy intensive production,biocompatibility etc. Lightweight and flexible magnets can be used for storage devices[30].

In Graphene,one must note that for magnetism in 2D systems,long range ordering in is very tough because of absence of d and f electrons. The observed magnetism is explained on the grounds of localised electronic states based on spin polarization.

4.6. Electrical Properties

Graphene is a zero band gap semiconductor with a very high electrical conductivity. Each carbon atom is connected to only three adjacent carbon atoms in sp[2] fashion leaving behind one electron free,which is responsible for conduction. The unhybridized p-orbitals of adjacent carbon in the same layer overlap to form n-bonds.

The unusual properties like chirality,ambipolar field effect, pseudospin, anomalous quantum Hall effect,high mobility of charge carriers and excellent thermal conductivity exhibited by graphene, beginning with 'tight-binding' approximately applied to model the band structure of graphite[31-32].

5. APPLICATIONS OF GRAPHENE FOR REAL-TIME APPLICATIONS

Graphene is considered to be a revolutionary material. The applications of graphene are truly endless, and lots of are yet to be conceived of [33-38]. In this section, few key applications of graphene are discussed in brief

5.1. Flexible Graphene Transistors

The graphene-based transistor may be a single electron nanoscale device, which involves the crossing of just one electron through it at once [33]. Such a transistor has evoked huge attention since its inception, and now many of them are within the marketplace for daily applications [33]. the most advantage of graphene­based transistors is that they will be operated easily at temperature and also have the potential to work at low voltage with high sensitivity [33]. These qualities make graphene-based transistors better than silicon­based transistors and that they also advance the microchip technology. Moreover, thanks to the intrinsic properties of graphene, such transistors are extremely flexible and foldable. The movement of electrons through graphene is 1000 to 10,000 times faster than in silicon. Therefore, it's far better than silicon in terms of electron mobility. However, pristine graphene can't be used as an alternate of silicon thanks to the bandgap issue. The electrons just in case of graphene behave like phonons which contrasts to their movement capabilities.

5.2. Graphene Sensors

A sensor may be a device that perceives actions that occur within the surroundings (like heat, motion, light, pressure, moisture, etc), and retorts with an output, usually with an optical, mechanical or electrical signal. The domestic mercury-in-glass thermometer may be a modest example of a daily used sensor. Graphene and sensors are natural combinations thanks to graphene's large surface-to-volume ratio, unique optical properties, excellent electrical conductivity, highcarrier mobility and density, high thermal conductivity etc. [36-38]. the massive area of graphene can enhance the surface loading of desired biomolecules. Its excellent conductivity and small bandgap are often beneficial for conducting electrons between biomolecules and therefore the electrode surface. an ideal sensor can distinguish minute changes in its encompassing condition because of the 2D, planar, and compatible settlement of particles during a graphene sheet. it's important to notice that, each particle inside the sheet is presented to the encircling condition [38,39]. This permits graphene to adequately recognize changes in its surroundings at micrometre measurements, giving a high level of affectability. Graphene is likewise able to distinguish singular perturbations on an atomic level [39]. a big number of graphene characteristics are helpful in sensor applications. As a whole, graphene might be utilized as a neighborhood of sensors in distinct areas consisting of bio-sensors, diagnostics, field­effect transistors, DNA sensors, and gas sensors [39].

5.3. Graphene for lithiumesulfur (LieS) battery

Different kinds of batteries including the lithium-sulfur battery, are fabricated since 1940 [40]. The demerits of the LieS battery and others is that it's expensive and therefore the lifetime is extremely short.

Generally, within the lithium-sulphur battery, sulphur act as cathode and lithium act as an anode. During the discharge of the lithiumsulphur battery, lithium is oxidized and converted into a lithiumion at the anode and at the cathode, sulfur is reduced and converted into a sulfur ion [40,41]. Then, the lithium ion moves towards the cathode to react with the reduced sulfur and forms Li2S. to unravel of these issues, graphene are often consolidated into both the anode and cathode in several battery frameworks to build the effectiveness of the battery and enhance the charge/ discharge cycle rate in many folds [40,41]. The superlative electrical conductivity, high aspect ratio, and dispersibility of graphene become much superior over the conventional inorganic-based cathode while mitigating the terminals of their constraints [40,41]. due to its adaptable behaviour, graphene has been frequently utilized in lithium-ion batteries, Li-S batteries, supercapacitors and energy components. Li-S batteries give energies up to 500 Wh/kg and even more for the real-time utilisation.Different kinds of batteries including the lithium-sulfur battery, are fabricated since 1940. The demerits of the LieS battery and others is that it's expensive and therefore the lifetime is extremely short.

Generally, within the lithium-sulphur battery, sulphur act as cathode and lithium act as an anode. During the discharge of the lithiumsulphur battery, lithium is oxidized and converted into a lithiumion at the anode and at the cathode, sulfur is reduced and converted into a sulfur ion [40,41]. Then, the lithium ion moves towards the cathode to react with the reduced sulfur and forms Li2S. to unravel of these issues, graphene are often consolidated into both the anode and cathode in several battery frameworks to build the effectiveness of the battery and enhance the charge/ discharge cycle rate in many folds [41]. The superlative electrical conductivity, high aspect ratio, and dispersibility of graphene become much superior over the conventional inorganic-based cathode while mitigating the terminals of their constraints due to its adaptable behaviour, graphene has been frequently utilized in lithium-ion batteries, Li-S batteries, supercapacitors and energy components. Li-S batteries give energies up to 500 Wh/kg and even more for the real-time utilisation [41]

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