Nanoparticles As A Advanced Drug Delivery System: World Journal of Pharmacy and Pharmaceutical Sciences March 2014

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NANOPARTICLES AS A ADVANCED DRUG DELIVERY SYSTEM
Article in WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES · March 2014
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WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
Shrivastava et al. World Journal of Pharmacy and Pharmaceutical Sciences
Volume 3, Issue 4, 479-499. Review Article ISSN 2278 – 4357
NANOPARTICLES AS A ADVANCED DRUG DELIVERY SYSTEM
Amit kr. Shrivastava*, Kiran Agrahari, Abhishek Singh, Prashant Singh, Dev Prakash
Kailash Institute of Pharmacy & Management Gida Gorakhpur

Uttar Pradesh, India.
ABSTRACT
Article Received on
24 February 2014, For the past few decades, there has been a considerable research
Revised on 13 March
2014, interest in the area of drug delivery using particulate delivery systems
Accepted on 31 March 2014
as carriers for small and large molecules.Particulate systems like
nanoparticles have been used as a physical approach to alter and
*Correspondence for Author
improve the pharmacokinetic and pharmacodynamic properties of
Amit kr. Shrivastava
various types of drug molecules. They have been used in vivo to
Kailash institute of pharmacy
& management gida gorakhpur protect the drug entity in the systemic circulation, restrict access of the
Uttar Pradesh, India. drug to the chosen sites and to deliver the drug at a controlled and
sustained rate to the site of action. Various polymers have been used in
the formulation of nanoparticles for drug delivery research to increase therapeutic benefit,
while minimizing side effects. Here, we review various aspects of nanoparticle formulation,
characterization, effect of their characteristics and their applications in delivery of drug
molecules and therapeutic genes.
Key words: Nanoparticles, drug delivery, targeting, drug release, microencapsulation.
INTRODUCTION
Nanoparticles are defined as particulate dispersions or solid particles with a size in the range
of 10-1000nm. The drug is dissolved,entrapped, encapsulated or attached to a nanoparticle
matrix. Dependingupon the method of preparation, nanoparticles, nanospheres
ornanocapsules can be obtained. Nanocapsules are systems in which the drug is confined to a
cavity surrounded by a unique polymer membrane, while nanospheres are matrix systems in
which the drug is physically and uniformly dispersed. In recent years, biodegradable
polymeric nanoparticles, particularly those coated with hydrophilic polymer such as poly
ethylene glycol (PEG) known as long-circulating particles, have been used as potential drug
www.wjpps.com Vol 3, Issue 4, 2014. 479

delivery devices because of their ability to circulate for a prolonged period time target a
particular organ, as carriers of DNA in gene therapy, and their ability to deliver. [ 1, 2 ]
proteins, peptides and genes. The major goals in designing nanoparticles as a delivery system
are to control particle size, surface properties and release of pharmacologically active agents
in order toachieve the site-specific action of the drug at the therapeutically optimal rate and
dose regimen. Though liposomes have been used as potential carriers with unique advantages
including protecting drugs from degradation, targeting to site of action and reduction toxicity
or side effects, their applications are limited due to inherent problems such as low
encapsulation efficiency, rapid leakage of water-soluble drug inthe presence of blood
components and poor storage stability. On the other hand, polymeric nanoparticles offer some
specific advantages over liposome’s. For instance, they help to increase the stability of
drugs/proteins and possess useful controlled release properties. The advantages of using
nanoparticles as a drug delivery system include the following: [ 3, 4 ]
 Particle size and surface characteristics of nanoparticles can be easily manipulated to

achieve both passive and active drug targeting after parental administration.
 They control and sustain release of the drug during the transportation and at the site of
localization, altering organ distribution of the drug and subsequent clearance of the drug
so as to achieve increase in drug therapeutic efficacy and reduction in side effects.
 Controlled release and particle degradation characteristics can be readily modulated by
the choice of matrix constituents. Drug loading is relatively high and drugs can be
incorporated into the systems without any chemical reaction; this is an important factor
for preserving the drug activity.
 Site-specific targeting can be achieved by attaching targeting ligands to surface of
particles or use of magnetic guidance.
 The system can be used for various routes of administration including oral, nasal,
parenteral,intra-ocular etc.
In spite of these advantages, nanoparticles do have limitations. For example, their small size
and large surface area can lead to particle - particle aggregation, making physical handling of
nanoparticles difficult in liquid and dry forms. 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. The present review details the latest development of nanopasrticulate drug delivery

systems, surface modification issues, drug loading strategies,release control and potential
applications of nanoparticles. [ 5, 6 ]
The technology can be applied to biological systems, or derivatives thereof, to make

nanomaterials for specific use. It incorporates a wider range of useful industrial and
biological processes that modify the needs of humanity at the nanoscale level. Studies have
also shown that microorganisms can as well be used as potential developers of NPs In view
of these developments, nanotechnological companies are gaining new prospects that enable
them to improve the performance of products and life with uncertain health safety issues.
However, the benefits of nanotechnology have been offset by substantial discussion about the
health issues arising from nanotechnologies [ 7,8 ] .Occupational illnesses, however, do occur
as a result of respiratory dust particle. This is attributed mainly to ultrafine NPs. These
occupational diseases tend to be characterized by temporal or permanent physiological
dysfunction with only a few visible symptoms. On the other hand, there is a possibility that
they may gain access to the body and pose serious toxicological problem. These NPs might
enter the host via the lungs, dermal, wound tissues, intestinal tract either intentionally or
unintentionally.NPs can enter the environment and animals system through different
pathways. For instance, it could be through effluent, spillage, consumer products and
disposal. The intake is usually tolerated by the organism system but when a certain range is
exceeded, it would cause toxic effect and even deaths. Since NPs have environmental and
animal health risks, it is, therefore, inevitable to carry out research so as to understand and
anticipate such risk through risk assessment and risk management. However, in view of
scarce health information arising from NPs, it is paramount to take some remedial actions so
as to reduce the hazards to workers and the environment.

Nanoparticles can be prepared from a variety of materials such as proteins, polysaccharides

and Synthetic polymers. The selection of matrix materials is dependent on many
factorsincluding:
1. size of nanoparticles required

2. inherent properties of the drug, e.g., aqueous solubility and stability
3. surface characteristics such as charge and permeability
4. degree of biodegradability, biocompatibility and toxicityDrug release profile desired;
5. Antigenicityof the final product. [ 9 ]
Polymers used in preparation of nanoparticles

The polymers should be compatible with the body in the terms of adaptability (non-toxicity)
and (non- antigenicity) and should be biodegradable and biocompatible. Natural polymers:
The most commonly used natural polymers in preparation of polymeric nanoparticles are:
 Chitosan
 Gelatin
 Sodium alginate
 Albumin
There are many synthetic polymers like

 Polylactides(PLA)
 Polyglycolides(PGA)
 Poly(lactide co-glycolides) (PLGA)
 Polyanhydrides
 Polyorthoesters
 Polycyanoacrylates
 Polycaprolactone
 Poly glutamic acid
 Poly malic acid
 Poly(N-vinyl pyrrolidone)
 Poly(methyl methacrylate)
Nanoparticles have been prepared most frequency by three methods:

 dispersion of preformed polymers
 Nanoprecipitation

 polymerization of monomers
 ionic gelation or coacervation of hydrophilic polymers.
Dispersion of preformed polymers:- Dispersion of preformed polymers is a common

technique used to prepare biodegradable nanoparticles from poly (lactic acid) (PLA); poly
(D,L-glycoside), PLG; poly (D, L-lactide-co-glycolide) (PLGA) and poly (cyanoacrylate)
(PCA), . This technique can be used in various ways as described below. [ 10, 11 ]
Solvent evaporation method:-In this method, the polymer is dissolved in an organic solvent
such as dichloromethane, chloroform or ethyl acetate which is also used as the solvent for
dissolving the hydrophobic drug. The mixture of polymer and drug solution is then
emulsified in an aqueous solution containing a surfactant or emulsifying agent to form an oil
in water (o/w) emulsion. After the formation of stable emulsion, the organic solvent is
evaporated either by reducing the pressure or by continuous stirring. Particle size was found
to be influenced by the type and concentrations of stabilizer, Homogenizer speed and
polymer concentrationIn order to produce small particle size, often a
High-speed homogenization or ultra sonicationmay be employed.
Fig. :- Schematic representation of the solvent-evaporation technique
Nanoprecipitation:- Nanoprecipitation is also called solvent displacement method. It

involves the precipitation of a preformed polymer from an organic solution and the diffusion
of the organic solvent in the aqueous medium in the presence or absence of a surfactant. The
polymer generally PLA, is dissolved in a water-miscible solvent of intermediate polarity,
leading to the precipitation of nanospheres. This phase is injected into a stirred aqueous

solution containing a stabilizer as a surfactant. Polymer deposition on the interface between

the water and the organic solvent, caused by fast diffusion of the solvent, leads to the
instantaneous formation of a colloidal suspension. To facilitate the formation of colloidal
polymer particles during the first step of the procedure, phase separation is performed with a
totally miscible solvent that is also a non-solvent of the polymer. The solvent displacement
technique allows the preparation of nanocapsules when a small volume of nontoxic oil is
incorporated in the organic phase. Considering the oil-based central cavities of the
nanocapsules, high loading efficiencies are generally reported for lipophilic drugs when
nanocapsules are prepared. The usefulness of this simple technique is limited to water-
miscible solvents, in which the diffusion rate is enough to produce spontaneous
emulsification. Then, even though some water-miscible solvents produce a certain instability
when mixed in water, spontaneous emulsification is not observed if the coalescence rate of
the formed droplets is sufficiently high. Although, acetone/dichloromethane (ICH, class 2)
are used to dissolve and increase the entrapment of drugs, the dichloromethane increases the
mean particle size and is considered toxic. This method is basically applicable to lipophilic
drugs because of the miscibility of the solvent with the aqueous phase, and it is not an
efficient means to encapsulate water-soluble drugs. This method has been applied to various
polymeric materials such as PLGA36, PLA43, PCL44, and poly (methyl vinyl ether-comaleic
anhydride) (PVM/MA). This technique was well adapted for the incorporation of cyclosporin
A, because entrapment efficiencies as high as 98% were obtained. Highly loaded
nanoparticulate systems based on amphiphilic h-cyclodextrins to facilitate the parental
administration of the poorly soluble antifungal drugs Bifonazole and Clotrimazole were
prepared according to the solvent displacement method. [ 12,1 ]

Schematic representation of the nanoprecipitation technique.

Surfactant is optional.
Solvent diffusionmethod:- This is a modified version of solvent evaporation method . In this
method, the watermisciblesolvent along with a small amount of thewater immiscible organic
solvent is used as anoil phase. Due to the spontaneous diffusion ofsolvents an interfacial
turbulence is created. Between the two phases leading to the formation of small particles. As
the concentration of water miscible solvent increases, a decrease in the size of particle can be
achieved.
Both solvent evaporation and solvent diffusion methods can be used for hydrophobic or
hydrophilic drugs. In the case of hydrophilic drug, a multiple w/o/w emulsion needs to be
formed with the drug dissolved in the internal aqueous phase.
Schematic representation of the emulsification/solvent diffusion technique
Spray Drying: -Spray-drying has been widely used for the production of micron-sized
particles. Spray-dry involves the conversion of a solution droplet into a dry particle by
evaporation of the solvent in a one-step process. Temperature –liable compounds such as
proteins and enzymes have been successfully spray-dried. It has been shown that particles
consisting of various polymers and drugs, both water –soluble and water-insoluble, can be
prepared without problem of drug leakage to another phase and thus, the recovery of drug in
the particles is almost the particle properties, especially morphology, can be controlled by the
solvent properties and the spray-drying variables. [ 2, 5 ]

Polymerization method: -In this method, monomers are polymerized toform nanoparticles
in an aqueous solution. Drugis incorporated either by being dissolved in thepolymerization
medium or by adsorption onto thenanoparticles after polymerization completed.The
nanoparticle suspension is then purified toremove various stabilizers and
surfactantsemployed for polymerization by ultracentrifugationand re-suspending the particles
in an isotonic surfactant-free medium. This technique has been reported for making
polybutylcyanoacrylate or poly (alkyl cyanoacrylate) nanoparticles. Nanocapsule formation
and their particle size depends on the concentration of the surfactants and stabilizers used.
Coacervation or ionic gelation method:-Much research has been focused on thepreparation

of nanoparticles using biodegradablehydrophilic polymers such as chitosan, gelatinand
sodium alginate. Calvo and co-workersdeveloped a method for preparing hydrophilicchitosan
nanoparticles by ionic gelation.The method involves a mixture of two aqueousphases, of

which one is the polymer chitosan, adi-block co-polymer ethylene oxide or propyleneoxide
(PEO-PPO) and the other is a polyanionsodium tripolyphosphate. In this method,positively
charged amino group of chitosaninteracts with negative charged tripolyphosphateto form
coacervates with a size in the range ofnanometer. Coacervates are formed as a resultof
electrostatic interaction between two aqueousphases, whereas, ionic gelation involves
thematerial undergoing transition from liquid to gel due to ionic interaction conditions at
roomtemperature.
[ 3, 13 ]
Ideal Properties of Polymeric Based Nps Are: -Natural or synthetic polymer

 Inexpensive Nontoxic
 Biodegradable
 Nonthrombogenic
 Nonimmunogenic
 No platelet aggregation
 Noninflammatory
 Prolonged circulation time
Types of Nanoparticles
 Quantum Dots
 Nanocrystalline Silicon
 Photonic
 Crystals
 Liposome

 Gliadin Nanoparticles
 Polymeric Nanoparticles
 Solid Lipid Quantum Nanoparticles (SLN)
 Others-gold,carbon,silver,etc. [ 15 ]
Quantum Dot: -A quantum dot is a semiconductor nanostructure that confines the motion
of conduction band electrons, valence band holes, or excitons (pairs of conduction band
electrons and valence band holes) in all three spatial directions. The confinement can be due
to electrostatic potentials (generated by external electrodes, doping, strain, impurities), due to
the presence of an interface between different semiconductor materials (e.g. in the case of
self-assembled quantum dots), due to the presence of the semiconductor surface (e.g. in the
case of a semiconductor nanocrystal), or to a combination of these. A quantum dot has a
discrete quantized energy spectrum. A quantum dot4 contains a small integer number (of the
order of 1-100) of conduction band electrons, valence band holes, or excitons, i.e., an integer
number of elementary electric charges.Small quantum dots, such as colloidal semiconductor
nanocrystals, can be as small as 2 to 10 nanometers, corresponding to 10 to 50 atoms in
diameter and a total of 100 to 100'000 atoms within the quantum dot volume. Self-assembled
quantum dots are typically between 10 and 50 nanometers in size. Quantum dots defined by
lithographically patterned gate electrodes, or by etching on two-dimensional electron gases in
semiconductor heterostructures can have lateral dimensions exceeding 100 nanometers6. At
10 nanometers in diameter, nearly 3 million quantum dots could be lined up end to end and fit
within the width of a human thumb.
Quantum dots can be contrasted to other semiconductor nanostructures
1) Quantum wires, which confine the motion of electrons or holes in two spatial directions
and allow free propagation in the third.
2) Quantum wells, which confine the motion of electrons or hles in one direction and allow
free propagation in two directions.
Quantum dots with a nearly spherical symmetry, or flat quantum dots with nearly cylindrical
symmetry can show shell filling according to the equivalent of Hund's rules for atoms. Such
dots are sometimes called "artificial atoms". In contrast to atoms, the energy spectrum of a
quantum dot can be engineered by controlling the geometrical size, shape, and the strength of
the confinement potential. Like in atoms, the energy levels of small quantum dots can be
probed by optical spectroscopy techniques. In quantum dots that confine electrons and holes,

the interband absorption edge is blue shifted due to the confinement compared to the bulk
material of the host semiconductor material. As a consequence, quantum dots of the same
material, but with different sizes, can emit light of different colors.[ 6, 7 ]
Quantum dots are particularly significant for optical applications due to their theoretically
high quantum yield. In electronic applications they have been proven to operate like a single-
electron transistor and show the Coulomb blockade effect. Quantum dots have also been
suggested as implementations of qubits for quantum information processing. Researchers at
Los Alamos National Laboratory have developed a wireless nanodevice that efficiently
produces visible light, through energy transfer from nano-thin layers of quantum wells to
nanocrystals above the nanolayers. Quantum dots are one of the most hopeful candidates for
solid-state quantum computation. By applying small voltages to the leads, one can control the
flow of electrons through the quantum dot and thereby make precise measurements of the
spin and other properties therein. Another cutting edge application of quantum dots is also
being researched as potential artificial fluorophore for intra-operative detection of tumors
using fluorescence spectroscopy. [14, 16 ]
Nanocrystalline silicon: -Nano crystalline siliconan allotropic form of silicon - is similar to

amorphous silicon (a-Si), in that it has an amorphous phase. Where they differ, however, is
that nc-Si has small grains of crystalline silicon within the amorphous phase. This is in
contrast to polycrystalline silicon (poly-Si) which consists solely of crystalline silicon grains,
separated by grain boundaries. Nc-Si is sometimes also known as microcrystalline silicon
(µc-Si)8 The difference comes solely from the grain size of the crystalline grains. Most
materials with grains in the micrometre range are actually fine-grained polysilicon, so
nanocrystalline silicon is a better term.
Nc-Si has many useful advantages over a-Si, one being that if grown properly it can have a
higher mobility, due to the presence of the silicon crystallites. It also shows increased
absorption in the red and infrared wavelengths, which make it an important material for use
in a-Si solar cells. One of the most important advantages of nanocrystalline silicon, however,
is that it has increased stability over a-Si, one of the reasons being because of its lower
hydrogen concentration.
Although it currently cannot attain the mobility that poly-Si can, it has the advantage over

poly-Si that it is easier to fabricate, as it can be deposited using conventional low temperature
a-Si deposition techniques, such as PECVD, as opposed to laser annealing or high
temperature CVD processes, in the case of poly-Si. [ 17, 9 ]
Photonic crystal: -Photonic crystals are periodic dielectric or metallo-dielectric

(nano)structures that are designed to affect the propagation of electromagnetic waves (EM) in
the same way as the periodic potential in a semiconductor crystal affects the electron motion
by defining allowed and forbidden electronic energy bands. The absence of allowed
propagating EM modes inside the structures, in a range of wavelengths called a photonic
band gap, gives rise to distinct optical phenomena such as inhibition of spontaneous
emission, high-reflecting omnidirectional mirrors and low-loss-wave guiding among others.
Since the basic physical phenomenon is based on diffraction, the periodicity of the photonic
crystal structure has to be in the same length-scale as half the wavelength of the EM waves
i.e. ~300 nm for photonic crystals operating in the visible part of the spectrum. This makes
the synthesis cumbersome and complex. To circumvent nanotechnological methods with their
big and complex machinery, different approaches have been followed to grow photonic
crystals as self-assembled structures from colloidal crystals. Photonic crystals are attractive
optical materials for controlling and manipulating the flow of light. They are of great interest
for both fundamental and applied research, and are expected to find commercial applications
soon.
Two-dimensionally periodic photonic crystals already have reached a level where integrated-
device applications are in sight, whereas their three-dimensional counterparts are still far
from commercialization but will offer additional advantages possibly leading to new device
concepts, when some technological aspects such as manufacturability and principal
difficulties such as disorder are under control. The first commercial products involving two-
dimensionally periodic photonic crystals are already available in the form of photonic-crystal
fibers, which use a nanoscale structure to confine light with radically different characteristics
compared to conventional optical fiber for applications in nonlinear devices, guiding exotic
wavelengths, and so on.
Liposome’s:-A liposome is a spherical vesicle with a membrane composed of a

phospholipids bilayer used to deliver drugs or genetic material into a cell. Liposome’s can be
composed of naturally-derived phospholipids with mixed lipid chains (like eg. ethanolamine),
or of pure components like DOPE .The lipid bilayer can fuse with other bilayers (e.g., the cell

membrane), thus delivering the liposome contents. By making liposome’s in a solution of

DNA or drugs, (which would normally be unable to diffuse through the membrane), they can
be (indiscriminately) delivered past the lipid bilayer. The use of liposomes for transformation
or transfection of DNA into a host cell is known as lipofection. Liposome’s can be created by
sonicating phospholipids in water.
Glidinnanoparticles: -In an effort to improve bioavailability anti-H.pylori effects of

antibiotics, mucoadhesive gliadin nanoparticles (GNP) which have the ability to deliver the
antibiotics at the sites of infection were prepared. GNP bearing clarithromycin (CGNP) and
omeprazole(OGNP) were prepared by desolvation method. In vivo gastric mucoadhesive
studies confirmed the strong mucoadhesive propensity and specificity and specificity of
gliadin nanoparticles towards stomach. Gliadin nanoparticles show a higher tropism for the
gastrointestinal regions and their presence in other intestinal regions is very low. This high
capacity to interact with the mucosa may be explained by gliadin composition. In fact, this
protein is rich in neutral and lipophilic residues. Neutral amino acid can promote hydrogen
bonding interaction with the mucosa whereas the lipophilic components can interact within
biological tissue by hydrophilic interaction. The related protein gliadin possessing an amino
and disulphide groups on the side chain has a good probability of developing bonds with
mucin gel.
Polymeric Nanoparticles: -Polymeric nanoparticles have been invented by Speiser et al.

They represent interesting alternative as drug delivery systems to liposomes.They usually
exhibit a long shelf life and a good stability on storage. These are superior to liposomes in
targeting them to specific organs or tissues by adsorbing and coating their surface with
different substances. Nanoparticles can be prepared either from preformed polymers, such as
polyesters (i.e. polylactic acid), or from a monomer during its polymerization, as in the case
of alkyl-cyanoacrylates Most of the methods based on the polymerization of monomers
consists in adding a monomer into the dispersed phase of an emulsion, an inverse
microemulsion, or dissolved in a non-solvent of the polymer. [ 5, 11, 19 ]
Solid Lipid Nanoparticles (SLN):-Solid lipid nanoparticles have been developed as

alternative delivery system to conventional polymeric nanoparticles.SLNs are sub-micron
colloidal carriers (50-1000nm) which are composed of physiological lipid, dispersed in water
or in an aqueous surfactant solution.15,16 SLNs combine advantages of polymeric

nanoparticles, fat emulsions and liposomes, but avoid some of their disadvantages.They are
biodegradable, biocompatible and non-toxic.
Nanoparticle size characterization

Particle Size Determination: -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 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.
Static Light Scattering: -Dynamic light scattering (DLS) is the name that covers different
techniques for measurement of particle size from the dynamic changes of the scattered light
intensity. Photon correlation spectroscopy (PCS) is at present the most widely used name. It
relates to the correlation technique that is most frequently applied in instruments. Quasi-
elastic light scattering (QELS) was used as a name often in the past. This term relates to the
type of interaction between particles and light. It is a rapid method for determining the mean
size, the size distribution and the polydispersity index (PdI) of a sample. In the DLS
technique, the intensity of the scattered light by an ensemble of particles is measured at a
given angle (90º) as a function of time. The Brownian motion of the dispersed particles
determines the rate of change of the scattered light intensity. The temporal intensity changes
are converted to a mean translational diffusion coefficient. Fast intensity changes are related
to a rapid decay of the correlation function and a large diffusion coefficient. The diffusion
coefficient is then converted into particle size by means of the Stokes–Einstein equation. DLS
measurement range is about 0.005–1 and time required for measurement is typically about
0.5–10 min. For measurement of large particles (larger than about 0.5 µm), three problems
are generally encountered are
 Particles may settle out of the measurement zone to the bottom of the cell and thus will
gradually become out of reach for measurement.
 Few particles suffice to reach the maximum allowable concentration in view of multiple
scattering and thus changes of their number concentration will bias the sizing result.
 Brownian motion is very slow, especially in liquids of increased viscosity. Thus, long
measurement times have to be applied, during which both instrument and suspension

should remain stable. Typically, the particulate concentration during measurement is

around 10-2 –10-3 % (v/v).
Scanning Electron Microscopy (SEM):-The scanning electron microscope (SEM) is a type

of electron microscope that images the sample surface by scanning it with a high-energy
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. The types of signals
produced by an SEM include secondary electrons, back-scattered electrons (BSE),
characteristic X-rays, light (cathodoluminescence), specimen current and transmitted
electrons. Secondary electron detectors are common in all SEMs, but it is rare that a single
machine would have detectors for all possible signals. The signals result from interactions of
the electron beam with atoms at or near the surface of the sample. In the most common or
standard detection mode, secondary electron imaging or SEI, the SEM can produce very
high-resolution images of a sample surface, revealing details about less than 1 to 5 nm in size.
Due to the very narrow electron beam, SEM micrographs have a large depth of field yielding
a characteristic three-dimensional appearance useful for understanding the surface structure
of a sample. This is exemplified by the micrograph of pollen shown to the right. A wide
range of magnifications is possible, from about 10 times (about equivalent to that of a
powerful hand-lens) to more than 500,000 times, about 250 times the magnification limit of
the best light microscopes. For the same reason, BSE imaging can image colloidal gold
immuno-labels of 5 or 10 nm diameter which would otherwise be difficult or impossible to
detect in secondary electron images in biological specimens. Characteristic X-rays are
emitted when the electron beam removes an inner shell electron from the sample, causing a
higher energy electron to fill the shell and release energy. [ 20, 21 ]
Transmission Electron Microscopy (TEM):-A transmission electron microscope is

analogous to a slide projector, with illumination from an electron beam rather than light.
When an electron beam is impinged upon a sample, a black and white TEM image is formed
from the passage of some electrons through the sample untouched, alongside the combination
of interactions between other electrons and sample atoms (e.g., inelastic/elastic scattering,
diffraction). If the UNdiffracted beam is selected to form the image, it is referred to as bright-
field imaging; in contrast, selection of strongly diffracting regions of the sample, which
would appear brighter than the transmitted beam, is known as dark-field imaging. It should

be noted that electrons may also be absorbed by molecules containing large atoms, or by
surface contamination (e.g., dust, grease). The absorption of a high density of electrons in a
specific region will cause a buildup of heat, leading to sample destruction and poor image
quality. Analogous to throwing a baseball of varying speeds through a wall, the relative
degree of penetration through a particular sample is governed by the energy of the electron
source. That is, higher energy electrons (e.g., 200 keV vs. 100 keV) will be more penetrating,
allowing for the characterization of thicker and/or less transparent samples. In general,
increasing the thickness of a sample, or decreasing the energy (i.e., accelerating voltage) of
the electron beam, will induce more scattering events through more effective interactions
between the electron beam and atoms of the sample. This effect will enhance image contrast,
since there is a larger deviation between the path lengths of transmitted and scattered
electrons that reach the viewing screen. However, this improvement of image quality is offset
by plentiful inelastic collisions that yield a broadened wavelength distribution of the electron
beam. Since individual electrons will have differing energies, they will be brought into focus
at different points resulting in a blurry image (i.e., decreased resolution). [ 22, 8 ]
Atomic Force Microscopy: In this technique, a probe tip with atomic scale sharpness is
raftered across a sample to produce a topological map based on the forces at play between the
tip and the surface. The probe can be dragged across the sample (contact mode), or allowed to
hover just above (noncontact mode), with the exact nature of the particular force employed
serving to Distinguish among the sub techniques. That ultrahigh resolution is obtainable with
this approach, which along with the ability to map a sample according to properties in
addition to size, e.g., colloidal attraction or resistance to deformation, makes AFM a valuable
tool. However, size and shape has been the most common application to date. The need to
raster the probe renders the method very time-consuming and the size of the sample actually
observed is small. Nanoparticles are typically presented as an evaporated suspension on
smooth silicon or mica surface, though not without the possibility of deformation.
Application of various forms of AFM to nanoparticles characterization represents an area of
active research.
X-Ray Diffraction (Power X-ray Diffraction):-The geometric scattering of radiation from

crystal planes within a solid allow the presence or absence of the former to be determined
thus permitting the degree of cry’s` telicity to be assessed. In one example; the crystallization
of interior lipids could be tracked. Application of the method is little different from that for

bulk powders, though broadening of the diffraction pattern’s peaks is observed for particles
less than 100nm in diameter. For nanoparticles, order on the smaller scale can be investigated
by reducing the wavelength and angle of incident radiation. Using electron or neutron beams
allows reduction of the former parameter due to the shorter De-Broglie wavelengths of such
particles.
Nuclear Magnetic Resonance Spectroscopy: Nuclear magnetic resonance (NMR) can be

used to determine both the size and the qualitative nature of nanoparticles. The selectivity
afforded by chemical shift complements the sensitivity to molecular mobility to provide
information on the physicochemical status of components within the nanoparticle. For
example; the mobility of Miglyol 812 within solid lipid nanoparticles confirmed the liquid-
like nature of the interior, though it was more limited than the same oil in an o/w emulsion.
Pulsed field gradient methods allow diffusivity of the entire particle to be quantified and
compared to produce 2-D, diffusion ordered plots in which colloidal behavior and chemical
speciation are leveraged simultaneously .In one case, the diffusion coefficient is used as a
surrogate for size of the nanoparticle with results that compare well to separation and DLS,
though only NMR could simultaneously detect micellar precursors. [ 23, 24 ]
Zeta Potential36: Zeta potential is used as a surrogate for surface change, and is often
measured by observing the oscillations in signal that result from light scattered by particles
located in an electric field, though there are other approaches. There are a number of
instrumental configurations by which this is achieved, mostly using a Doppler shift, and the
user should familiarize them with the particular approach implemented in their equipment.
Instrumentation concerns aside, the need for dilution begs the question of what is an
appropriate diluents, because its choice can profoundly influence the surface chemistry and
thus the results. One approach is to use a particle-free supernatant to dilute the sample. This
will not account for concentration effects, however, and obtaining such a diluents is
nontrivial as the particle size drops. Electro acoustic methods should in principal eliminate or
reduce the need for dilution and its inevitable consequences. Non polar media and the
combination of low mobility with high ionic strength are also problematic; however, phase
analysis light scattering, a newer method in which a phase delay shift rather than a frequency
shift is observed, addresses these issues. [ 2 ]

Advantage of nanoparticles
 Nanoparticles have dimensions below the critical wavelength of light renders them
transparent, a property which makes them very useful for applications in packagings,
cosmetics and coatings.
 Particle size and surface characteristics of nanoparticles can be easily manipulated to
achieve both active and passive targeting.
 Release of the drug can be controlled or sustained so as to achieve increase in therapeutic
efficacy of drug and reduction in side-effects.
 They are capable of being stored for a period of upto 1 year and hence have longer shelf
stability.
 They have the ability to incorporate both hydrophilic and hydrophobic drug molecules.
 They have higher carrier capacity and drugs can be incorporated without any chemical
reaction and hence preserving the drug activity.
 The system can be administered via different routes including oral, nasal, parenteral etc.
 These have the potential to increase the bioavailability of drugs.
 They have longer clearance time.
 Site-specific targeting can be achieved by attaching targeting ligands to surface of
particles or by using magnetic guidance.
Disadvantage of nanoparticles
 It involves higher manufacturing costs which may in turn lead to increase in the cost of
formulation.
 These have low encapsulation efficiency.
 Water-soluble drugs can be rapidly leaked out in the presence of blood components.
 Their small size and large surface area can lead to particle-particle aggregation, making
physical handling of nanoparticles difficult in dry and liquid forms.
 They may trigger immune response and allergic reaction.
 It may involves use of harsh toxic solvents in the preparation process. [ 1, 3 ]
Therapeutic application of nanoparticles

Nanoparticles have been widely employed for different therapeutic applications, some of
which are listed below
 For intracellular targeting of anti-effective drugs to combat the difficult to treat’
intracellular infections of the human body.

 For targeting of cytostatic drugs to reduce toxicity and increase therapeutic activity.
 For specific targeting of anti-inflammatory drugs to areas of inflammation, by which the
side-effects of these drugs can be minimized.
 For ocular delivery systems, to deliver pilocarpine and other mitotic drugs.
 As carriers for radio nucleotides for diagnostic purposes in nuclear medicines.
 To improve the solubility and bioavailability of poorly soluble drugs and protects from
gastrointestinal enzymes and hence, helps in peroral absorption.
 For skin and hair care in the form of solid nanoparticles, wherein the oily core contains a
wide variety of different cosmetic oils and lipophilic agents.
 To deliver drugs across the blood brain barrier (BBB).
 To formulate sustained release preparations.
 For the controlled delivery of disinfectants or algicide into large bodies of water such as
insect pest feed.
 For targeted delivery of proteins and peptides.
 As adjutants to render antigens potent enough to be useful for vaccines.
 Have prolonged systemic drug effect due to prolonged systemic circulation and hence,
uptake by reticuloendothelial system can be avoided. [ 2 ]
CONCLUSION
Nanoparticles are the colloidal particles whose size ranges in the nanometric size which are
mainly employed through parenteral route, hence, requiring careful development of test
methods and acceptance criteria for the specifications. The foregoing shows that
nanoparticulate systems have great potentials, being able to convert poorly soluble, poorly
absorbed and labile biologically active substance into promising deliverable drugs.To
optimize this drug delivery system, greater understanding of the different mechanisms of
biological interactions, and particle engineering, is still required. Further advances are needed
in order to turn the concept of nanoparticletechnology into a realistic practical application as
the next generation of drug delivery system. In particular, the in vitro release test method and
acceptance criteria require rigorous scientific consideration and should be developed with an
eye toward understanding the mechanisms of drug release. The final specifications need to
ensure the safety, identity, strength, performance, and quality of the drug product at release
and during storage through the end of its shelf-life. The objective of nanoparticulate system is
to achieve a desired pharmacological response in a sustained manner at a selected site without

undesirable interactions at the other sites. This is especially important in cancer

chemotherapy, enzyme replacement therapy etc.
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1. Remington the science and practice of pharmacy Volume 2nd Lippincott Williams &
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Dadar Bombay.
4. Mu L, Feng SS. A novel controlled release formulation for the anticancer drug paclitaxel
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5. Kreuter J. Nanoparticles. In Colloidal drug delivery systems, J, K., Ed. Marcel Dekker:
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6. Reverchon E, Adami R. Nanomaterials and supercritical fluids. The Journal of
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7. Rolland JP, Maynor BW, Euliss LE, Exner AE, Denison GM, DeSimone JM. Direct
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wirtschaftlicher Wachstumsmarkt, 2004, accessed on 13 November 2008.
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carriers for oral peptide delivery. J. Control. Release 1990; 13: 233-239.
17. Maynard, A.D., ´Nanotechnology: the next big thing, or much ado about nothing?´, Ann.
Occup. Hyg, 2006, 1–12.
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strategiesfor safety evaluation of nanomaterials, part VII: evaluating consumer exposure
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NANOPARTICLES AS A ADVANCED DRUG DELIVERY SYSTEM

Article in WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES · March 2014

Amit Kumar Shrivastava Abhishek Singh

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NANOPARTICLES AS A ADVANCED DRUG DELIVERY SYSTEM

Kailash Institute of Pharmacy & Management Gida Gorakhpur

Key words: Nanoparticles, drug delivery, targeting, drug release, microencapsulation.

www.wjpps.com Vol 3, Issue 4, 2014. 479

 Particle size and surface characteristics of nanoparticles can be easily manipulated to

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The technology can be applied to biological systems, or derivatives thereof, to make

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Nanoparticles can be prepared from a variety of materials such as proteins, polysaccharides

1. size of nanoparticles required

Polymers used in preparation of nanoparticles

There are many synthetic polymers like

Nanoparticles have been prepared most frequency by three methods:

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Dispersion of preformed polymers:- Dispersion of preformed polymers is a common

Fig. :- Schematic representation of the solvent-evaporation technique

Nanoprecipitation:- Nanoprecipitation is also called solvent displacement method. It

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solution containing a stabilizer as a surfactant. Polymer deposition on the interface between

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Schematic representation of the nanoprecipitation technique.

Schematic representation of the emulsification/solvent diffusion technique

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Coacervation or ionic gelation method:-Much research has been focused on thepreparation

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Ideal Properties of Polymeric Based Nps Are: -Natural or synthetic polymer

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Nanocrystalline silicon: -Nano crystalline siliconan allotropic form of silicon - is similar to

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Photonic crystal: -Photonic crystals are periodic dielectric or metallo-dielectric

Liposome’s:-A liposome is a spherical vesicle with a membrane composed of a

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membrane), thus delivering the liposome contents. By making liposome’s in a solution of

Glidinnanoparticles: -In an effort to improve bioavailability anti-H.pylori effects of

Polymeric Nanoparticles: -Polymeric nanoparticles have been invented by Speiser et al.

Solid Lipid Nanoparticles (SLN):-Solid lipid nanoparticles have been developed as

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Nanoparticle size characterization

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should remain stable. Typically, the particulate concentration during measurement is

Scanning Electron Microscopy (SEM):-The scanning electron microscope (SEM) is a type

Transmission Electron Microscopy (TEM):-A transmission electron microscope is

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X-Ray Diffraction (Power X-ray Diffraction):-The geometric scattering of radiation from

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Nuclear Magnetic Resonance Spectroscopy: Nuclear magnetic resonance (NMR) can be

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Therapeutic application of nanoparticles

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