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Nanotechnology defined as a tiny science.
Now a day, there has been an exponential interest in the development of novel
drug delivery systems using nanoparticles. Several techniques are used for
preparation of nanoparticles like Solvent evaporation, Double emulsification
method, Emulsions - diffusion method, Nano precipitation, Coacervation method,
Salting out method, Dialysis and supercritical fluid technology. This review
focuses on various synthesis and preparation methods of nanoparticles.
Keywords:
Nanotechnology, Nanoparticles, Synthesis of nanoparticles, Preparation
techniques
INTRODUCTION
Nanoparticles
can be defined as objects ranging in size from 1-100 nm that due to their size
may differ from the bulk material [1]. Nanoparticles are defined as particulate
dispersions or solid particles drug carrier that may or may not be
biodegradable [2]. Nanoparticles are having application in various fields of
life sciences such as separation technologies, histological studies, clinical
diagnostic assays and drug delivery systems [3]. 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 to achieve
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 in the presence of blood components and poor storage
stability [4].
SYNTHESIS OF NANOPARTICLES
Nanoparticles can be synthesized chemically or biologically. Many adverse effects have been associated with chemical synthesis methods due to the presence of some toxic chemical absorbed on the surface. Eco-friendly alternatives to chemical and physical methods are biological ways of nanoparticles synthesis using microorganisms, enzymes, fungus and plants or plant extracts [5-8].
Biosynthesis
of nanoparticles
Biosynthesis of
nanoparticles by microorganisms is a green and eco-friendly technology. Diverse
microorganisms, both prokaryotes and eukaryotes are used for synthesis of
metallic nanoparticles [9]. The synthesis of nanoparticles may be intracellular
or extracellular according to the location of nanoparticles [10].
Intracellular synthesis of
nanoparticles by microbes
This method
involves transport of ions into microbial cells to form nanoparticles in the
presence of enzymes. As compared to the size of extracellularly reduced
nanoparticles, the nanoparticles formed inside the organism are smaller. The
size limit is probably related to the particles nucleating inside the organisms
[11].
Extracellular synthesis of
nanoparticles by microbes
Extracellular
synthesis of nanoparticles has more applications as compared to intracellular
synthesis since it is void of unnecessary adjoining cellular components from
the cell. Mostly, fungi are known to produce nanoparticles extracellularly because of
their enormous secretory
PREPARATION TECHNIQUES
Solvent evaporation
Solvent
evaporation method first developed for preparation of nanoparticles [12].
Polymer dissolved in organic solvent. Drug is dispersed in this solution. Then
this mixture emulsified in an aqueous phase containing surfactant make an ion
in water emulsion by using mechanical stirring, sonication or micro
fluidization. After formation of emulsion the organic solvent evaporates by
increased the temperature and reduced pressure with continuous stirring [13].
Double emulsification method
Double
emulsification technique is prepared by addition of aqueous drug solution to
organic polymer solution with continuous stirring. This prepared emulsion
another aqueous phase with vigorous stirring, results emulsion prepared, then
organic solvent removed by high centrifugation [14].
Emulsions - Diffusion method
In this method
polymer dissolved in water-miscible solvent and saturated with water.
Polymer-water saturated solvent phase is emulsified in an aqueous solution
containing stabilizer. Then solvent removed by evaporation or filtration [15].
Nano precipitation method
In this method
precipitation of polymer and drug obtained from organic solvent and the organic
solvent diffused in to the aqueous medium with or without presence of
surfactant. Firstly drug was dissolved in water and then solvent was added into
this solution. Then another solution of polymer and propylene glycol with
chloroform prepared and this solution was dispersed to the drug solution. This
dispersion was slowly added to 10 ml of 70% aqueous ethanol solution. After 5
min of mixing, the organic solvents were removed by evaporation at 35° under
normal pressure, nanoparticles were separated by using cooling centrifuge,
supernatant were removed and nanoparticles washed with water and dried at room
temperature in a desiccator [16].
Coacervation method
By using
biodegradable hydrophilic polymers nanoparticle prepared by Coacervation
method. This nanoparticle was prepared by ionic gelation method which
involves two aqueous phases. First phase contain polymer like chitosan, a
di-block co-polymer like ethylene oxide or propylene oxide. Second phase
contain polyanion sodium tripolyphosphate. Between these two phases
electrostatic interaction occurs which forms coacervates [17]. Drug and protein
solution (2% w/v) incubated for one hour at room temperature and pH adjusted to
5.5 by using 1 M HCl. In this solution ethanol was added in 2:1 ratio (v/v) in
a control rate 1 ml/min. Resultant coacervate hardened with 25% glutaraldehyde
(1.56 μg/mg of protein) for 2 h which allow cross-linking of protein. Rotary
vacuum evaporation at reduced pressure organic solvents were removed then
nanoparticle were collected and purified by centrifugation at 4°C. Pellets of
nanoparticles were then suspended in phosphate buffer (pH 7.4;
Salting
out method
This technique
based on the separation of water-miscible solvent from aqueous solution by
salting out effect. In this method toxic solvents are not used. Polymer and
drug dissolved in a solvent which emulsified into a aqueous solution containing
salting out agent but salting out can also be produced by saturation of the
aqueous phase using colloidal stabilizer/emulsion stabilizer/viscosity
increasing agent such as polyvinyl pyrrolidone or hydroxyethylcellulose, PVA,
PLGA and poly(trimethylene carbonate). After preparation of o/w emulsion
diluted with addition of sufficient water to allow the complete diffusion of
acetone into the aqueous phase, thus inducing the formation of nanospheres.
This technique does not require an increase in temperature and stirring energy
required for lower particle size. Disadvantage of this technique is exclusive
application to lipophilic drug and the extensive nanoparticles washing steps [15].
Dialysis
Dialysis is an
effective method for preparation of nanoparticles. In this method firstly
polymer and drug dissolved in an organic solvent. This solution added to a
dialysis tube and dialysis performed against a non-solvent miscible with the
former miscible. The displacement of the solvent inside the membrane is
followed by the progressive aggregation of polymer due to a loss of solubility
and the formation of homogeneous suspensions of nanoparticles. Dialysis
mechanism for formation of nanoparticle is not fully understood at present. It
may be based on a mechanism similar to that of nanoprecipitation [16].
Supercritical fluid technology
Supercritical
fluid technology method is alternative method because in this method organic
solvents are not used which are hazardous to the environment as well as to
physiological systems. Supercritical fluids define as a solvent at a
temperature above its critical temperature at which the fluid remains a single
phase regardless of pressure.
Mainly
supercritical fluid used in two main techniques:
1) Supercritical
anti-solvent (SAS)
2) Rapid expansion of critical solution (RESS)
Super critical anti-solvent
In SAS process
liquid solvents are used, which should completely miscible with the
supercritical fluid. The process of SAS employs a liquid solvent, e.g.
methanol, which is completely miscible with the supercritical fluid, the
extract of the liquid solvent by supercritical fluid leads to the instantaneous
precipitation of the solute, it results the formation of nanoparticles [18].
Rapid expansion of critical
solution
In RESS high
degree of super saturation occur by dissolving solute in a supercritical fluid
to form a solution, followed by the rapid expansion of the solution across an
orifice or a capillary nozzle into ambient air by the rapid pressure reduction
in the expansion which results in homogenous nucleation and thereby, the
formation of well-dispersed particles [15].
CONCLUSION
Nanoparticle
technologies have great potentials, being able to convert poorly soluble,
poorly absorbed and labile biologically active substance into promising
deliverable substances. Nanoparticle is novel approach for drug delivery which
we can achieve better therapeutic action, better bioavailability, reduce
toxicity. Today nanoparticles are successfully used in brain targeting, in
cancer therapy, etc.
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