eISSN: 2320-1428
Int.J.Inv.Pharm.Sci.,1(1)2013;81-84 www.ijips.net
INTERNATIONAL JOURNAL OF INVENTIONS IN PHARMACEUTICAL SCIENCES A NOVEL REVIEW IN NANOPHARMA TECHNOLOGY-SOLID LIPID NANOPARTICLES SK.RAZIYABEGUM1*, M.MOHANVARMA1, M.MADAN MOHANREDDY2, E.ANKARAO3, D.MAHIDHAR REDDY4, K. JYOTHIRMAI4 1
ShriVishnu College of Pharmacy, Bhimavaram 2 Eisai pharmatechnologyvizag, 3 Hetero Drugs, 4 Narayana pharmacy college Nellore,
Accepted On: 28thJanuary 2013
For correspondence:
[email protected]
ABSTRACT: Solid lipid nanoparticles (SLN) are rapidly developing colloidal drug delivery systems in the field of nanotechnology. Due to their unique sizedependent properties, lipid nanoparticles offer the possibility to develop new therapeutics. An incorporation of drugs into these nanocarriers offers drug targeting. Hence, there is a tremendous research is going on SLN toreach the goal of controlled and site specific drug delivery. In this article we focused on advantages, different preparation methods which are suitable for large scale production, evaluation and application of SLNs. Key Words: Solid lipid nanoparticles, homogenization, microscopy, targeting.
INTRODUCTION: Colloidal carriers ranging in size between 10 and 1000 nm are
MERITS OF SLN:
known as nanoparticles.They are manufactured from natural or
Controlled and site specific drug delivery
synthetic polymers and ideally suited to optimize drugdelivery and
Good biocompatible
reduce toxicity. The scarcity of safe polymers with regulatory
More sensible for higher drug loading
approval and their high cost have limited application of
Improve the stability of bioactive compounds
nanoparticles toclinical medicine. To overcome these limitations of
Enhance the bioavailability of entrapped pharmaceuticals
polymeric nanoparticles, lipids have been put forward as an
Chemical protection of bioactive compounds
alternative carrier, particularly for poorly water soluble drugs.
Easy to scale up and sterilize
These lipid nanoparticles areknown as solid lipid nanoparticles.In order to overcome the disadvantages associated with the liquid state
Production of SLNs:
of the oil droplets, the liquidlipid was replaced by a solid lipid,
SLNs are prepared using lipid, emulsifier and water/solvent by
which
employing various methods like
eventually
nanoparticlesSubmicron
transformed colloidal
into
carrier
range
solid
lipid
50-1000nm,
composed of solid hydrophobic core having a monolayer coating of
1.
High pressure homogenization.
phospholipids.Solid lipid nanoparticles (SLN) introduced in 1991
a)
Hot homogenization.
represent an alternative carrier system totradition colloidal carriers
b)
Cold homogenization.
such as - emulsions, liposomes and polymeric micro and
2.
nanoparticles.
Unique Properties of SLN:
Emulsification methods a)
Micro emulsion method
b)
Double emulsion method
3.
Ultrasonication or high speed homogenization. Precipitation method
Small size
4.
Large surface area
5.
Spray drying method
High drug loading
6.
Supercritical fluid method
Their potential to improve performance of
1. High pressure homogenization
pharmaceuticals
High pressure homogenization technique is very efficient for the
.
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production of SLNs. This method is easy to handle. High pressure
homogenizers push a liquid with high pressure (100–2000 bar)
by stirring the lipid and an aqueous emulsifier solution at high
through a narrow gap. The fluid accelerates on a very short
speed and high temperature conditions. Finally SLNs are produced
distance to very high velocity (over 1000 Km/h). Very high shear stress and disrupt the particles down to the submicron
by dispersing the warm w/o emulsion in an aqueous stabilizer
range.generally this method is divided into hot and cold
solution (w/o/w) at 2-30C under high speed stirring conditions.
homogenization. 3. Ultrasonication or high speed homogenization: 1a) Hot homogenization: Hot homogenization is carried out at
It is very simple and it can be advantageous over other method
temperatures above the melting point of the lipid. First
like hot and cold homogenization because the equipment used in
disperse/dissolve drug in the melted lipid and then add this mixture
this technique is very common in every lab. The main drawbacks
to the hot aqueous surfactant solution using stirring device. The
of this method are broader particle size distribution, particle
obtained pre emulsion is homogenized at higher pressure to get hot
growth upon storage and contamination of metal due to
o/w nanoemulsion. Finally SLNs after cooling of above solution to
ultracentrifugation
room temperature. In most cases 3-5 homogenization cycles at 5001500 bar are sufficient8. Increasing the homogenization leads to an
4. Precipitation method :The glycerides are dissolved in an
increase of the particle size due to particle coalescence which
organic solvent (e.g. chloroform) and the solution will be
occurs because of the high kinetic energy of the particles. The main
emulsified in an aqueous phase. After evaporation of the organic
drawbacks of this method is High temperature lead to degradation
solvent the lipid will be precipitatedforming nanoparticles. The
of active compound and Partitioning and hence loss of drug into the
main disadvantage is need of an organic solvent
aqueous phase during homogenization. 5. Spray drying method: 1b) Cold homogenization: Cold homogenization has been
It is a cheaper procedurethan lyophilization to prepare SLNs. This
developed to overcome various problems associated with hot
method cause particle aggregation due to high temperature, shear
homogenization. First disperse/dissolve drug in the melted lipid and
forces and partial melting of the particle. The best result was
solidif9ied the mixture using liquid nitrogen/dry ice. The solidified
obtained with SLN concentration of 1% in a solution of trehalose
mixture grinded to fine particles using powder mill and this is
in water or 20% trehalose in ethanol-water mixtures (10/90 v/v)
disperse in a cold surfactant solution using stirrer. The obtained pre suspension is homogenized at higher pressure and at below room
6. Supercritical fluid method:
temperature to get SLNs. Compared to hot homogenization; larger
This is a new method and advantage of solventless technique.
particle sizes and a broader size distribution is typical of cold
SLNs can be prepared by the rapid expansion of supercritical
homogenized samples. Cold homogenization minimizes the thermal
carbon dioxide (99.99%) solutions
7,8
exposure of the sample . EVALUATION OF PREPARED SLNS: 2a) Micro emulsion method: This method is based on the dilution of microemulsions. As micro-emulsions are two-phase systems
1. Entrapment efficiency
composed of an inner (disperse phase) and outer phase (continuous
2. In Vitro assessment of drug release from SLNs
phase).The transparent system obtained by adding a mixture of
3. Analytical characterization of SLNs
water, emulsifier, co- emulsifier to the melted lipid at higher
A)Particle size and zeta potential
temperature under mild stirring condition. The hot micro emulsion
B)Surface element analysis
0
is dispersed in cold water (2-3 ) under stirring.Typical volume
4. stability of SLNs
ratios of the hot micro emulsion to cold water are in the range of 1:25 to 1:50.
1. Entrapment efficiency: It influences the release characteristics of drug from SLNs.
2b) Double emulsion method:It is a novel method for the
The amount of drug encapsulated per unit weight of SLNs is
production of hydrophilic loaded SLNs.W/O emulsion is obtained
determined after separation of the entrapped drug from the
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SLN formulation. This separation can be carried out using the
particles is collected and fit into fundamental
different techniques like ultracentrifugation and centrifugation
primary variable.
filtration. 2.
7.
In vitroAssessment of drug release from SLNs:
Dynamic Light Scattering(DLS): DLS, also known as PCS or quasi-elastic light scattering (QELS)
Dialysis tubing: In vitro drug release can be carried out using
records the variation in the intensity of scattered
dialysis tubing. The solid lipid nanoparticles dispersionis
light on the microsecond time scale. The advantages
placed in pre - washed dialysis tubing which can be
of the method are the speed of analysis, lack of
hermetically sealed. The dialysis sac then dialyzedagainst a
required
suitable dissolution medium at room temperature; the samples
micrometer particles.
are withdrawn from the dissolutionmedium at suitable
8.
calibration,
and
sensitivity
to
sub
Acoustic Spectroscopy: It measures the attenuation
intervals, centrifuged and analyzed for the drug content using a
of sound waves as a means of determining size
suitable analyticalmethod.
through the fitting of physically relevant equations.
b)
ANALYTICAL CHARACTERIZATION OF SLNS:
Surface elemental analysis:It is characterized by using different techniques like Electrophoresis and Laser Doppler anemometry.
a)
Particle size and zeta potential:
1.
Photon Correlation Spectroscopy: Also known as
2.
STABILITY OFSLNS:
dynamic light scattering method. This technique
The physical properties of SLN’s during prolonged storage can be
measures the fluctuation of the intensity of the
determined by monitoring changes in zeta potential, particle size,
scattered
particle
drug content, appearance and viscosity as the function of time.
movement. PCS is a good tool to characterize
External parameters such as temperature and light appear to be of
nanoparticles, but it is not able to detect larger micro
primary importance for long – term stability. The zeta potential
particles.
should be in general, remain higher than -60mV for a dispersion to
Electron
light
which
is
Microscopy:
caused
by
Scanning
electron
remain physically stable.
microscopy (SEM) and Transmission electron microscopy (TEM) are the direct method to measure nanoparticles,
physical
characterization
of
nanoparticles with the former method being used for
3.
6.
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An adjuvant for vaccines: Adjuvants are used in vaccination to enhance the immune response. Being in
Atomic Force Microscopy (AFM): A probe tip
the solid state, the lipid components of SLNs will be
with atomic scale sharpness is rastered across a
degraded more slowly providing a longerlasting exposure
sample to produce a topological map based on forces
to the immune system. 2.
As Targeted anticancer drug carriers: Tumor targeting
Differential Scanning Calorimetry (DSC): DSC
has been achieved with SLN loaded with drugs like
can be used to determine the nature and speciation of
methotrexate, Tamoxifen and camptothecin.
crystallinity within nanoparticles. 5.
1.
morphological examination.
at play between the tip and the surface. 4.
POTENTIAL APPLICATIONS OF SLNS:
3.
To deliver the proteins and peptides: Proteins and
Nuclear Magnetic Resonance (NMR): NMR is
antigens intended for therapeutic purposes may be
used to determine both size and nature of
incorporated or adsorbed onto SLN, and further
nanoparticles.
administered by parenteral routes or by alternative routes (SLS)/Fraunhofer
such as oral, nasal and pulmonary. A, insulin, calcitonin
Diffraction: The method is fast and rugged. In this
and somatostatin have been incorporated into solid lipid
method the light scattered from a solution of
particles and are currently under investigation.
Static
Light
Scattering
4.
As targeted brain drug delivery: SLNs can improve the ability of the drug to penetrate through the BBB and is a promising drug targeting system for the treatment of CNS disorders.
5.
As gene vector carrier: There are several recent reports of SLN carrying genetic/peptide materials such as DNA, plasmid DNA and other nucleic acids.
6.
As cosmeceuticals:The SLNs have been applied in the sunscreen preparations and as an active carrier agent for molecular sunscreens and UV blockers.
7.
For potential agriculture application: Essential oil extracted from ArtemisiaarboreseensL when incorporated in SLN, were able to reduce the rapid evaporation comparedwith emulsions and the systems have been used in agriculture as a suitable carrier of ecologically safe pesticides.
CONCLUSION: Solid lipid nanoparticles are combining the advantage of other colloidal drug carriers and rectify the disadvantages of them. SLNs have the potential to achieve, at least partially, these broad objectives. Apart from these, the regular objective of controlled drug delivery is aptly achieved with SLNs.Clear advantages of SLN include the composition (physiological compounds), the rapid and effective production process including the possibility of large scale production, the avoidance of organicsolvents and the possibility to produce carriers with higher encapsulation efficiency . Hence, in the future we can expect more patented dosage forms in the form of SLNs.
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