an overview on nanotechnology

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Divya et al. World Journal of Pharmacy and Pharmaceutical Sciences

AN OVERVIEW ON NANOTECHNOLOGY

P. Divya*, Dr. A. Seetha Devi and M. Sri Rekha

India.

ABSTRACT

This chapter explores the basic definitions for nanotechnology, and

sketches a concept system for the field. Nano biotechnology is the

application of nanotechnology in biological fields. Nanotechnology is

a multidisciplinary field, which covers a vast and diverse array of

devices derived from engineering, biology, physics and chemistry.

The associated research and applications are equally diverse, ranging

from extensions of conventional physics to completely new

approaches based upon developing new materials with new dimensions on Nano scale.

Nanotechnology explores electrical, optical, and magnetic activity as well as structural

behavior at the molecular and sub molecular level. It has the potential to revolutionize a

series of medical and biotechnology tools and procedures so that they are portable, cheaper,

safer and easier to administer. The nanoparticles are generally classified into the organic,

inorganic and carbon based particles in nanometric scale that has improved properties

compared to larger sizes of respective materials. The nanoparticles show enhanced properties

such as high reactivity, strength, surface area, sensitivity, stability, etc. because of their small

size. The nanoparticles are synthesized by various methods for research and commercial uses

that are classified into three main types namely physical, chemical and mechanical processes

that has seen a vast improvement over time.

KEY WORDS: Nano particles, Method of preparation, Applications.

INTRODUCTION

Nanotechnology is the science of matter and material that deals with the particle size in

nanometers (1nm=10-9

m). The term „nano‟ is derived from Latin word, which means dwarf.

Nanotechnology deals with design, characterization and application of various structures,

devices systems by controlling the size and shape at nanometric scale. Pharmaceutical

Nanotechnology embraces applications of nano science to pharmacy as nanomaterials, and as

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 8, Issue 12, 292-308 Review Article ISSN 2278 – 4357

Article Received on

10 Oct. 2019,

Revised on 30 Oct. 2019,

Accepted on 20 Nov. 2019,

DOI: 10.20959/wjpps201912-14920

*Corresponding Author

P. Divya

India.

https://www.sciencedirect.com/topics/earth-and-planetary-sciences/nanotechnology


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devices like drug delivery, diagnostic, imaging and biosensor materials. Pharmaceutical

nanotechnology has provided more fine-tuned diagnosis and focused treatment of disease at

molecular level. It helps in detecting the antigen associated with diseases such as cancer,

diabetes mellitus, neurodegenerative diseases, as well as detecting the microorganisms and

virus associated with infections.

The size of the nanoparticle structure may ranges from upto 1 to 100nm in at least one

dimension. However, the prefix “Nano” is commonly used for particles that are up to several

hundred nanometres in size the drug is dissolved, entrapped, encapsulated or attached to this

nanoparticle matrix. Depending upon the method of preparation, nanoparticles, nanospheres

or nanocapsules can be obtained. Nanoparticles, particularly coated with hydrophilic polymer

such as poly ethylene glycol (PEG) known as long-circulating particles, used as a potential

drug delivery devices because of their ability to circulate for a prolonged period of time,

target to a particular organ, such as carrier of DNA in gene therapy.

bio nanotechnology, the incorporation of biological molecules into Nano artifacts. The

discovery of some of the mechanistic details of complicated biological machinery such as the

ribosome, which encodes the sequence of nucleic acids as a sequence of amino acids,

promotes assembler-based view of nanotechnology, and these biological machines provided a

kind of living proof of principle that elaborate and functionally sophisticated mechanisms

could operate at the Nanoscale. The highly refined molecular binding specificity is

particularly valued, and used to facilitate the assembly of unique structures from a solution of

precursors and for capturing chemicals from the environment prior to registering their

presence via a transducer (biosensors). A further application involves using the widely

encountered ability of biomolecules to easily accomplish actions associated with difficult and

extreme conditions in the artificial realm, such as the catalysis of many chemical reactions,

and optical nonlinearity with single photons, a feature which can be exploited to construct

optical computers. One might also mention the kidneys as a marvelous example of biological

Nano engineering that functions to extract certain substances from highly dilute solutions, an

operation which may become of increasing importance as conventionally processable ores

become depleted.[1,4]

Advantages

1. Increased surface area, oral bioavailability and rate of dissolution.

2. Decreases the dose of the drug required and reduces the number of doses.

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3. Reduced mortality and morbidity rates and increased longevity in return.[5]

4. Nanotechnology is seen as a boon in the medical world, since these can help in creating

new drugs.

5. Nanotechnology could also be used to refine drug production, tailoring drugs at a

molecular level to make them more effective and reduce side effects.[6]

Different Nano Drug Delivery Systems Developed Using Nanotechnology Principles are

1. Nanoparticles.

2. Solid lipid nanoparticles.

3. Nanocrystals.

4. Nanosuspensions.

5. Nanoemulsions.

6. Nanospheres.

7. Nanocapsules.

8. Nanosponges.

Nanoparticles

Nanoparticles are defined as particulate dispersions or solid particles with a size in the range

of 10-1000nm.[7]

It‟s Coarse particles range between 10,000 and 2,500 nanometers. Fine

particles are in size range between 2,500 and 100 nanometers. Ultrafine particles or

nanoparticles are sized between 1 and 100 nanometers.[8]

The drug is dissolved, entrapped

and encapsulated or attached to this nanoparticle matrix.

Nanoparticles can be of two types depending upon the method of preparation:

1. Nanospheres: These have monolithic type system (matrix) in which drugs are either

adsorbed or dispersed.

2. Nanocapsules: In these drugs are adsorbed on to their exterior or entrapped in the core

also these particles exhibit a membrane wall structure.[9]


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Figure 1: Types of nanoparticles.

Types of Nanoparticles[10]

Figure 1.1: Types of nanoparticles.

Advantages of Nanoparticles

1. Both passive and active drug targeting after parenteral administration can be easily

manipulated to achieve particle size and surface characteristics of nanoparticle.

2. The drug release may be controlled or sustained during the transportation at the site of

localization, which alters the organ distribution of the drug in order to achieve maximum

therapeutic efficacy and reduce the side effects.[11]

3. By the choice of matrix constituents like controlled release and particle degradation

characteristics can be readily modulated.[12]

4. They can be easily administered by various routes including nasal, oral, parenteral etc.

5. Drug loading in nanoparticles is relatively high as compared to other dosage forms.


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6. Reduction in toxicity is also an important advantage of nanoparticles.

7. Use of nanoparticle can reduce dosing frequency thus increasing bioavailability of

drug.[13]

Preparation of Nanoparticles

Nanoparticles are aimed to be prepared from a variety of materials such as proteins,

polysaccharides and synthetic polymers. The selection criteria of matrix materials depends

on many factors such as: (a) Size of nanoparticles required; (b) Inherent properties of the

drug, e.g. aqueous solubility and stability; (c) Surface characteristics such as Charge and

Permeability; (d) Degree of biodegradability, biocompatibility and toxicity; (f)Antigenicity of

the final product.[14]

Nanoparticles are prepared by various methods of preparation including

1) Solvent evaporation method

2) Solvent diffusion method

3) Phase inversion temperature method

4) Super critical fluid method

5) Salting out

6) Spray drying

7) Polymerization method

8) Emulsification method

Solvent evaporation method: The polymer and hydrophobic drug is dissolved in an organic

solvent for solvent evaporation method. Oil in water (o/w) emulsion is formed when the

mixture of polymer and drug solution is added to the aqueous solution containing a surfactant

or emulsifying agent. The organic solvent is evaporated from the stable emulsion either by

reducing the pressure or by continuous stirring. The type and concentrations of stabilizer,

homogenizer speed and polymer concentration shows the effect on particles size. In order to

produce small particle size, often a high-speed homogenization or ultra-sonication may be

employed.[15]


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Solvent diffusion method[16]

Figure 2: solvent diffusion method.

Phase inversion temperature method

In this process droplets of Nano emulsion are used to de solubilise the polymer to produce

nanoparticles. In this method polymer had been introduced earlier to produce Nano-emulsion,

the oil is substituted by volatile solvent, the nanoparticles are produced After that solvent

evaporation takes place below PIT. Main advantage of this method is that organic solvent is

lost there is no other interest to change the Phase Inversion Temperature.[17]

Super critical fluid method

To prepare biodegradable micro- and nanoparticles the supercritical fluid technology has

been used, because they are environmentally safe. Supercritical CO2 (SC CO2) is the most

widely used supercritical fluid because of its mild critical conditions nontoxicity,

nonflammability and low price. The most common processing techniques involving

supercritical fluids are supercritical anti solvent (SAS) and rapid expansion of critical

solution (RESS). The liquid solvent is employed in the process of SAS, eg: methanol, which

is completely miscible with the supercritical fluid (SC CO2), to dissolve the solute to be

micronized; at the process conditions, the solute is insoluble in the supercritical fluid, the

instantaneous precipitation of the solute is formed due to the extract of the liquid solvent by

the super critical fluid, resulting for the formation of nanoparticles. RESS differs from the

SAS process in that its solute is dissolved in a supercritical fluid and then the solution is

rapidly expanded through a small nozzle into a region lower pressure, Thus the solvent power


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of supercritical fluids dramatically decreases and the solute eventually precipitates. the

precipitate in this technique is basically solvent free.. Supercritical fluid technology

technique, is environmentally friendly and suitable for mass production, requires specially

designed equipment and it is more expensive.[18]

Salting out: Salting out is a modified formulation of emulsion process in fabricating polymer

encapsulated lipophilic drug via salting-out agent. In this preparation, polymer and drug are

dissolved in water soluble solvent such as acetone, ethanol, and methanol whereas aqueous

medium contains gel with stabilizer and high concentration of salting-out agent. The common

choices of salting-out agents used in electrolytes are magnesium chloride, calcium chloride as

well as magnesium acetate. In a nonelectrolyte system, sucrose is utilized. Polymer and drug

are emulsified in aqueous gel forming oil-in-water emulsion under high mechanical stirring.

Subsequently, the emulsion is diluted in adequate volume of water to enrich the diffusion of

solvent into aqueous phase, decreasing the ionic strength in the electrolyte. This step induced

hardened polymers. The solvent is then removed via reduced pressure, followed by

ultracentrifugation and repeated washing to eliminate both salting-out agent and stabilizer to

yield NPs.

The main distinction from the conventional emulsion diffusion method is the presence of

solvent diffusion step due to the presence of salting agent. In this process, salting-out agents

play prominent role in manufacturing polymer encapsulated drugs NPs. The salts initially

impede the miscibility of organic phase into aqueous solution, forming emulsion.

Subsequently, reverse salting-out effect leads to precipitation, which aided in entrapment of

drug into the polymer matrix, forming the NPs. Thus, the advantages of employing this

technique are high yield, excellent efficiency of drug encapsulation, small particle size, and

feasible production scaling up. Moreover, an increase of temperature is not needed

consequently may be useful when heat sensitive substances have to be processes.[19]

Spray drying: spray dryers refer to using spray drying to create particles in the nanometer

range. Spray drying is a gentle method for producing powders with a defined particle size out

of solutions, dispersions, and emulsions which is widely used for pharmaceuticals, food,

biotechnology, and other industrial materials synthesis.

In the past, the limitations of spray drying were the particle size (minimum 2micrometres),

the yield (maximum around 70%), and the sample volume (minimum 50ml for devices in lab

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https://www.sciencedirect.com/topics/materials-science/polymer

https://www.sciencedirect.com/topics/materials-science/polymer-matrix

https://en.wikipedia.org/wiki/Spray_drying

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scale). Recently, minimum particle sizes have been reduced to 300nm, yields up to 90% are

possible, and the sample amount can be as small as 1 ml. These expanded limits are possible

due to new technological developments to the spray head, the heating system, and the

electrostatic particle collector. To emphasize the small particle sizes possible with this new

technology, it has been described as "nano" spray drying. However, the smallest particles

produced are in the sub-micrometric range common to fine particles rather than the

nanometer scale of ultrafine particles.[20]

Polymerization method

In this method, nanoparticles are formed in an aqueous solution, due to polymerization of

monomers. Dissolving in the polymerization medium or by adsorption onto the nanoparticles

drug is in-corparated after polymerization completed. The nanoparticle suspension is then

purified to remove various stabilizers and surfactants employed for polymerization by

ultracentrifugation and re-suspending the particles in an isotonic surfactant-free medium.

This technique has been reported for making polybutyl cyanoacrylate or poly

(alkylcyanoacrylate) nanoparticles.[21]

Emulsification method

Another method which can be used for preparation of nanoparticles is the emulsification

diffusion method. The method utilizes a partially water-soluble solvent like acetone or

propylene carbonate. The polymer and the drug are dissolved in the solvent and it is

emulsified in the aqueous phase containing the stabilizer. The role of stabilizer prevents the

aggregation of emulsion droplets by adsorbing of the surface of the droplets. Addition of

water to the emulsion, allow the diffusion of the solvent into the water. The solution is stirred

leading to the nano precipitation of the particles. Further, it can be collected by

centrifugation, or the solvent can be removed effectively by dialysis. The main problem with

this method is that the water soluble drugs tend to leak out from the polymer phase during

diffusion steps. So, in order to avoid this problem the dispersing medium changed from

aqueous medium to medium chain triglycerides and a small amount of surfactant is added

into it. The Nano particles are collected from the oily suspension by centrifugation.[22]

Evaluation of Nanoparticles

Particle size

Particle size and size distribution are the most important characteristics of nanoparticle

systems. They determine the in vivo distribution, biological fate, toxicity and the targeting

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300


ability of nanoparticle systems. In addition, they can also influence the drug loading, drug

release and stability of nanoparticles. Many studies have demonstrated that nanoparticles of

sub-micron size have a number of advantages over microparticles as a drug delivery

system.[23]

Generally nanoparticles have relatively higher intracellular uptake compared to

microparticles and available to a wider range of biological targets due to their small size and

relative mobility. Desai et al found that 100nm nanoparticles had a 2.5fold greater uptake

than 1µm microparticles, and 6 fold greater uptake than 10µm microparticles in a Caco-2 cell

line.[24]

In a subsequent study[25]

, the nanoparticles penetrated throughout the submucosal

layers in a rat in situ intestinal loop model, while micro particles were predominantly

localized in the epithelial lining. It was also reported that nanoparticles can across the blood-

brain barrier following the opening of tight junctions by hyper osmotic mannitol, which may

provide sustained delivery of therapeutic agents for difficult-to-treat diseases like brain

tumors.[26]

Tween 80 coated nanoparticles have been shown to cross the blood-brain

barrier.[27]

In some cell lines, only submicron nanoparticles can be taken up efficiently but not

the larger size micro particles.[28]

Drug release is affected by particle size. Smaller particles have larger surface area, therefore,

most of the drug associated would be at or near the particle surface, leading to fast drug

release. Whereas, larger particles have large cores which allow more drug to be encapsulated

and slowly, diffuse out.[29]

Smaller particles also have greater risk of aggregation of particles

during storage and transportation of nanoparticle dispersion. It is always a challenge to

formulate nanoparticles with the smallest size possible but maximum stability.

Polymer degradation can also be affected by the particle size. For instance, the rate of PLGA

polymer degradation was found to increase with increasing particle size in vitro.[30]

It was

thought that in smaller particles, degradation products of PLGA formed can diffuse out of the

particles easily while in large particles, degradation products are more likely remained within

the polymer matrix for a longer period to cause autocatalytic degradation of the polymer

material. Therefore, it was hypothesized that larger particles will contribute to faster polymer

degradation as well as the drug release. However, Panyam et al prepared PLGA particles with

different size ranges and found that the polymer degradation rates in vitro were not

substantially different for different size particles.[31]

Currently, the fastest and most routine method of determining particle size is by photon-

correlation spectroscopy or dynamic light scattering. Photon-correlation spectroscopy


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requires the viscosity of the medium to be known and determines the diameter of the particle

by Brownian motion and light scattering properties.[32]

The results obtained by photon-

correlation spectroscopy are usually verified by scanning or transmission electron microscopy

(SEM or TEM).

Drug Entrapmaent Efficiency

The nanoparticles were separated from the aqueous medium by ultracentrifugation at 10,000

rpm for 30 min at 50C. Then the resulting supernatant solution was decanted and dispersed

into phosphatebuffer saline pH 7.4. Thus the procedure was repeated twice to remove the

unentrapped drug molecules completely. The amount of drug entrapped in the nanoparticles

was determined as the difference between the total amount of drug used to prepare the

nanoparticles and the amount of drug present in the aqueous medium. Drug Entrapment

efficiency (%) = Amount of released from the lysed nanoparticle X 100 Amount of drug

Initially taken to prepare the Nanoparticles.[33]

Zeta potential

The Zeta potential of a nanoparticle is commonly used to characterized the surface charge

property of nanoparticles. It reflects the electrical potential of particles and is influenced by

the composition of the particle and the medium in which it is dispersed. Nanoparticles with a

zeta potential above (±) 30 mV have been shown to be stable in suspension, as the surface

charge prevents aggregation of the particles.[34]

SEM analysis

Further characterization was done by Scanning Electron Microscope (SEM). The diameter of

the Silver nano particles was determined. A scanning electron microscope (SEM) is a type of

electron microscope that images a sample by scanning it with a beam of electrons in a raster

scan pattern. The electrons interact with the atoms that make up the sample producing signals

that contain information about the sample's surface topography, composition, and other

properties such as electrical conductivity.[35]

Compatibility Studies: Compatibility in drug and polymer is the main issue in the

formulation. The drug should be compatible with polymers which are being used. The

compatibility of drug with adjuvants can be determined by Thin Layer Chromatography

(TLC) and Fourier Transform Infra-red Spectroscopy (FT-IR).[36]


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Resiliency: To determine the viscoelastic properties of nanoparticle. Viscoelastic properties

of particle is modified to produce beedlets which are softer and firmer when needed for final

formulation. When cross linking got increased and tends to slow down rate of release.

Resiliency are studied according to requirement by releasing function of cross-linking with

time.[37]

Dissolution tests : Dissolution profile of nanoparticle are studied using dissolution apparatus

USP having a modified basket consist of 5ml stainless steel mesh with a speed of rotation

around 150rpm. Proper dissolution medium is selected and solubility of active contents are

considered to ensure sink conditions. Proper analytical method are used for the sample form

dissolution medium(38)

Particle Shape

The nanoparticles were subjected to microscopic examination (SEM) for characterization

size. The nanosuspension was characterized by SEM before going for evaluation; the

nanosuspension was lyophilized to form solid particles. The solid particles were coated with

platinum alloy using a sputter coater.[38]

Limitations of Nanoparticles

1. Small size and large surface area can lead to particleparticle aggregation, making physical

handling of nanoparticles difficult in liquid and dry forms.

2. In addition, small particles size and large surface area readily result in limited drug

loading and burst release. These practical problems have to be overcome before

nanoparticles can be used clinically or made commercially available.[39.40]

Applications of Nano particle

Cancer therapy

Photodynamic cancer therapy is based on the destruction of the cancer cells by laser

generated atomic oxygen, which is cytotoxic. A greater quantity of a special dye that is used

to generate the atomic oxygen is taken in by the cancer cells when compared with a healthy

tissue. Hence, only the cancer cells are destroyed then exposed to a laser radiation.

Unfortunately, the remaining dye molecules migrate to the skin and the eyes and make the

patient very sensitive to the daylight exposure. This effect can last for up to six weeks.


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To avoid this side effect, the hydrophobic version of the dye molecule was enclosed inside a

porous nanoparticle.[41]

The dye stayed trapped inside the Ormosil nanoparticle and did not

spread to the other parts of the body. At the same time, its oxygen generating ability has not

been affected and the pore size of about 1 nm freely allowed for the oxygen to diffuse out.

Protein detection

Proteins are the important part of the cell's language, machinery and structure, and

understanding their functionalities is extremely important for further progress in human

wellbeing. Gold nanoparticles are widely used in immunohistochemistry to identify protein-

protein interaction. However, the multiple simultaneous detection capabilities of this

technique are fairly limited. Surface-enhanced Raman scattering spectroscopy is a well-

established technique for detection and identification of single dye molecules. By combining

both methods in a single nanoparticle probe one can drastically improve the multiplexing

capabilities of protein probes. The group of Prof. Mirkin has designed a sophisticated

multifunctional probe that is built around a 13nm gold nanoparticle. The nanoparticles are

coated with hydrophilic oligonucleotides containing a Raman dye at one end and terminally

capped with a small molecule recognition element (e.g. biotin). Moreover, this molecule is

catalytically active and will be coated with silver in the solution of Ag (I) and hydroquinone.

After the probe is attached to a small molecule or an antigen it is designed to detect, the

substrate is exposed to silver and hydroquinone solution. A silver-plating is happening close

to the Raman dye, which allows for dye signature detection with a standard Raman

microscope. Apart from being able to recognise small molecules this probe can be modified

to contain antibodies on the surface to recognise proteins. When tested in the protein array

format against both small molecules and proteins, the probe has shown no cross-reactivity.[42]

Tissue Engineering

The natural bone surface in most cases contains features that are approximately 100nm

across. If an artificial bone implant‟s surface is smooth, the body will reject it. By creating

nano-sized features on the surface of the knee or hip prosthesis, the chances of rejection can

be reduced. The production of osteoblasts can also be simulated, this was demonstrated using

ceramic, polymeric, and recently, metal materials. These findings could help to design a

robust and long-lasting hip or knee replacements and reduce the chances of the implant

becoming loose.[42]


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Energy and Electronics

Researchers are exploring the use of nanotechnology to generate more efficient and cost-

effective energy. When sunlight is concentrated on nanoparticles, it creates steam with high

energy efficiency.

Similarly, high-efficiency light bulbs can be produced with a nano-engineered polymer

matrix in a specific style. These innovative bulbs are shatterproof and have double the

efficiency of fluorescence light bulbs.

Attempts are also being made to develop high-efficiency LEDs using arrays of nano-sized

structures known as plasmonic cavities. Similarly, windmill blades are being developed using

epoxy containing carbon nanotubes. These nanotube-filled epoxies help to create stronger yet

lightweight blades, which boost the amount of electricity produced by individual windmills.

Nanotube sheets have also been used to create thermocells, which produce electricity when

the cell sides are at varying temperatures. These nanotube sheets can be enclosed around a

car‟s exhaust pipe to produce electricity from heat which is otherwise wasted.

Nanotechnology is employed in many different electronics, communications, and computing

applications, providing smaller, faster, and more portable systems. These systems can store

large amounts of data.

Some examples of nanoelectronics are cell phone castings, flash memory chips for iPod

nano's, antibacterial and antimicrobial coatings on keyboard and mouse, etc. Nanotechnology

is used in smart cards, printed electronics for RFID, and smart packaging, as well as in

flexible displays for e-book readers and life-like video games.

It is even used in nanoscale transistors that are more powerful, faster, and highly energy-

efficient. In the future, the entire memory of a computer may be stored on a just one small

chip.

Other uses of nanotechnology include next-generation televisions, plasma displays, digital

cameras, laptops, quantum computers, magnetic random access memory, and organic light-

emitting diodes (OLEDs). Nanotechnology is set to redefine many electronic products,

processes, and applications in future.[43]


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