NEED OF NANOPARTICLES
OTHER TYPE OF NANOPARTICLES
The word ‘Nano’ is derived from Latin word,
which means “dwarf” (1nm=10-9m).
Nanotechnology is science of the small , the
very small used to prepare matter at tiny scale.
“FUTURE OF TECHNOLOGY”
The Nobel prize in physics (1965) winner “RICHARD FEYMAN” is known as “FATHER OF
NANOTECHNOLGY” published the paper of “THERE’S PLENTY OF ROOM AT BOTTOM”.
Over a decade later, Professor “NORIO TANIGUCHI” actually coined the term
Nanoparticles as a drug delivery vehicle were first developed by “Spieser and co-workers”
in the early 1980s.(NANOPELLETS AND MICROPELLETS)
6. NANOPARTICLES -DEFINITION
Nanoparticles are sub-nanosized colloidal drug
delivery system .
Its size ranges from 1-100nm in diameter.
They are composed of synthetic or semi synthetic
polymers carrying drugs or proteinaceous
substances, i.e. antigen(s).
The first reported nanoparticles were based on
non-biodegradable polymeric systems.
7. NEED OF NANOPARTICLES
Nanoparticles are of interest because of new properties that they exhibit compared with larger particles
of the same materials.
Eg: TiO2,ZnO become transparent at nanoscale
The major goal of designing nanoparticles as a delivery system are to control particle size and release
of pharmacologically active agents in specific site at controlled rate.
Reduction in the
frequency of the
Drug loading is high
IN CANCER CHEMOTHERAPY, CYTOSTATIC DRUGS DAMAGE BOTH MALIGNANT AND
NORMAL CELLS . BUT NANODRUG DELIVERY SELECTIVELYTARGETS MALIGNANT
TUMOR CELLS ONLY…..
High manufacturing cost
Large volume of solvent is utilized
Physical handling of particles is difficult
Difficult to maintain stability of dosage form
Reduced ability to adjust the dose
Requires skills to manufacture
11. IDEAL CHARACTERSTICS
Biochemically inert, non toxic ,non- immunogenic.
Restrict drug distribution to non target cells or tissues or organs & should have uniform
Controllable and predictable rate of drug release.
Carrier used must be biodegradable or readily eliminated from the body without any
It should be stable both physically and chemically in in-vivo and in-vitro condition.
12. POLYMERS USED IN PREPARATION OF NANOPARTICLES
15. PREPARATION TECHNIQUES OF NANOPARTICLES
The selection of the appropriate method for the preparation of nanoparticles depends on ,
1)Physicochemical characteristics of the polymer
2)Drug to be loaded
Drug may be added during preparation of nanoparticles or to the previously prepared
16. APPROACHES APPLIED
The “top-down” approach, which involves the breaking down of large pieces of material to
generate the required nanostructures from them.
The “bottom-up” approach, which implies assembling single atoms and molecules into larger
20. 1) AMPHIPHILIC MACROMOLECULE CROSS-LINKING
Nanoparticles can be prepared from amphiphilic macromolecules, proteins and
polysaccharides (which have affinity for aqueous and lipid solvents).
Technique of their preparation involves:
Aggregation of amphiphiles
(by HEAT OR CHEMICAL
Emulsification using high-pressure homogenization or high frequency
Surfactant W/O emulsion
Poured in preheated oil above100oC or chemical cross linking agent
Stirred to form
Centrifugation and isolation of
22. 2) POLYMER PRECIPITATIONMETHODS
In these methods, the hydrophobic drug or a hydrophobic polymer is dissolved in a particular
organic solvent followed by its dispersion in a continuous aqueous phase, in which the
The external phase also contains the stabilizer.
They are 4 types
a. Emulsion Solvent evaporation method
b. Double emulsion Solvent evaporation method
c. Solvent displacement method
d. Salting out method
23. A) EMULSION-SOLVENT EVAPORATION METHOD
Organic Solvents: Dichloromethane,
Chloroform, Ethyl acetate.
Evaporation is done by reducing the pressure
pressure or by continuous stirring.
Stabilizers - polysorbates, poloxamers,
sodium dodecyl sulphate.
Homogenizer speed, nature and stabilizer
concentration along with the property of
polymer effect size of nanoparticle.
Suitable for lipid soluble drugs.
25. B)DOUBLE EMULSION SOLVENT EVAPORATIONS METHOD
Suitable for Hydrophilic drugs
Nanoparticles are separated by
centrifugation at high speed
26. C) SOLVENT DISPLACEMENT /PRECIPITATION METHOD
Drug,polymer,surfactant dissolved in
Aq.phase with stabilizer
Immediate polymer precipitation because
of complete miscibility of both the phase.
Diffusion of organic phase during stirring
28. D) SALTING OUT OF POLYMER
Aqueous phase :Distilled water
Organic Phase: Acetone
Stabilizer: Poly vinyl Alcohol
Salting out agent: Magnesium chloride,
Suitable for drug & polymers that are
soluble in polar solvent such as acetone or
ethanol, heat sensitive drugs .
30. 3) POLYMERIZATION METHODS
Monomers are polymerized to form nanoparticles in an aqueous solution in
which drug may be dissolved.
Drug may also be incorporated by absorption onto the nanoparticles after
Eg : Polybutylcyanoacrylate nanoparticles
a) Emulsion polymerization
b) Dispersion polymerization
31. A) EMULSION POLYMERIZATION
Emulsion polymerization: - this method involves emulsification of
monomer in non-solvent phase.
It may be conventional or reverse, depending upon nature of continuous
Conventional method= Continuous phase is aqueous(O/W emulsion)
Reverse method= Continuous phase is organic (W/O emulsion)
Dissolve lipophilic monomer in water then add surfactant with hydrophilic heads and lipophilic tails
Formed micelles in water
Lipophilic monomer escape from water and enter the lipophilic core of micelles
Add “RADICAL INITIATOR” ,which enter micelles and force monomer to form a polymer via polymerisation
Then the micelles dissociate and the polymer chains are attached to each other 32
34. B)DISPERSION POLYMERIZATION
-Monomer is dissolved in the Aq medium, which acts as a precipitant for formed polymer.
-Nucleation is directly induced in Aq. Monomer solution.
-So STABILIZER/ SURFACTANT is no needed
Here initiation is achieved by different mechanism, but mostly it is by irradiating solution with high
(Gamma, UV, strong visible light).
36. 1) SOLID LIPIDNANOPARTICLES (SLNS)
These are a new generation of submicron-sized lipid emulsions where the liquid lipid (oil) has
been substituted by a solid lipid.
SLNs offer unique properties such as small size, large surface area, high drug loading &
the interaction of phases at the interfaces, & are attractive for their potential to improve
performance of Pharmaceuticals, Nutraceuticals & other materials.
1) Control & target drug release
2) Good biocompatibility
3) Feasibility of carrying both lipophilic & hydrophilic drugs
4) High & enhanced drug content when compared to other carriers
5) Improves the stability of pharmaceuticals
6) Low toxicity
38. PREPARATIONOF SOLID-LIPIDNANOPARTICLES
SLNs are made up of solid lipid, emulsifier & water/solvent.
The lipids used may be triglycerides, partial glycerides, fatty acids, steroids & waxes.
Various emulsifiers & their combinations like pluronic F68, F 127 can be used to stabilize the
39. DIFFERENT METHODS OF PREPARATION OF SLNS
A) High pressure homogenization
- Hot homogenization
- Cold homogenization
B) Ultra sonication/high speed homogenization
C) Solvent emulsification/evaporation
D) Double emulsion method
E) Micro emulsion based SLNs preparations
F) SLNs preparation by using supercritical fluid
G) Spray drying method
40. A) HIGHPRESSURE HOMOGENIZATION
This technique was initially used for the production of solid-lipid Nano dispersions.
Lipids used in this study are tripalmitin, mixture of mono, di glycerides (witepsolW35).
Glycerol behenate & poloxamer 188 as steric stabilizers (0.5% w/w).
By using Witepsol W35 dispersions the best SLNs quality was obtained after stirring for 8min
at 20,000 rpm followed by cooling for 10min & stirring at 5000 rpm at a room
41. HOT HOMOGENIZATION
Dissolution of the drug in melted lipid
Premix using a stirrer to form a coarse
High-pressure homogenization at a
temperature above the lipid melting point
O/W Nano emulsion
Solidification of nano-emulsion by cooling at room
43. B) ULTRASONICATION OR HIGH SPEED HOMOGENIZATION
In this method the SLNs are produced by high speed stirring or sonication.
1) Equipment used is very common
2) No temperature induced drug degradation
Physical instability like particle growth upon storage.
44. C) SOLVENT EMULSIFICATION/EVAPORATIONMETHOD
In this method, lipophilic material is dissolved in water immiscible organic solvent (e.g.,
cyclohexane) that is emulsified in an aqueous phase to give oil/water (o/w) emulsion.
On evaporation of the solvent under reduced pressure, solid lipid nanoparticles dispersion is
Adv:- Avoidance of any thermal stress.
Disadv:- use of organic solvents.
45. D) DOUBLE EMULSION METHOD
This method is modification of emulsion solvent evaporation.
Organic solvent, drug and distilled water form the W/O emulsion by sonication or
homogenization and stabilized at 4 oC.
Adding the aqueous phase with stabilizer to form double emulsion W/O/W.
Evaporation of solvent to form SLNs.
Washed and lyophilised.
It is used for the preparation of hydrophilic loaded SLNs.
46. E) MICROEMULSIONBASED SLNS PREPARATION
A warm micro emulsion is prepared by stirring, containing typically 10%
molten solid lipid, 15% surfactant & upto 10% co-surfactant.
This warm micro emulsion is then dispersed under stirring in excess cold
water (typical ratio 1:50) using thermostated syringe.
The excess water is removed either by ultrafiltration or by lyophilisation
in order to increase the particle concentration.
47. F) BY USING SUPERCRITICAL FLUID
This is a new technique for SLNs production.
SLNs can be prepared by the rapid expansion of supercritical carbon
dioxide solutions (Rapid Expansion of Supercritical Solution) method.
Carbon dioxide (99.99%) is a good choice as a solvent for this method.
48. G) SPRAY DRYING METHOD
The lipid is first dissolved in suitable volatile organic solvent.
The drug in solid form is then dispersed in the solution under high speed homogenization.
This dispersion is then atomized in a stream of hot air.
The atomization leads to formation of droplets from which solvent evaporate instantly to form SLN.
This method causes particle aggregation due to high temperature shear forces & partial melting
of the particle.
Recommended use of lipid with M.P >700 c for spray drying.
49. 2) DRUG NANOCRYSTALS
Drug Nanocrystals are crystals with a size in the nanometre range, which means they are nanoparticles
with a crystalline character.
A further characteristic is that drug nanocrystals are composed of 100% drug; there is no carrier
material as in polymeric nanoparticles.
Nanocrystals also possess advantages of increased bioavailability & increase in saturation solubility.
51. A. MILLING METHOD
Small milling pearls or large milling balls are used
as milling media.
With a reduction in the size of grinding media in a
media mill, the number of contact points is
increased results in improved grinding leads to
The balls consist of ceramic, stainless steel or
highly cross linked polystyrene resin coated beads.
52. B. PRECIPITATION METHOD
A poor water-soluble drug is dissolved in an organic solvent, which is water miscible.
Pouring of solution into a non-solvent, such as water, leading to the precipitation of finely
dispersed drug nanocrystals.
A problem associated with this technology is that the formed nanoparticles need to be
stabilized to avoid growth in micrometer crystals.
53. C. HOMOGENIZATIONMETHOD
Three technologies are used for preparation of nanocrystals by homogenization methods
Micro fluidizer technology,
Piston gap homogenization in water,
Piston gap homogenization in water mixtures or non aqueous media.
54. 3) NANOSUSPENSIONS
Pharmaceutical Nano suspension is defined as very finely dispersed solid drug particles in
an aqueous vehicle.
The particle size in Nano suspension ranges between 200 - 600nm.
Stabilized by surfactant .
Dispersion of drug nanocrystals in liquid media leads to “nanosuspensions”.
Dispersion media can be water, aqueous solutions or non aqueous media (e.g., liquid
polyethylene glycol (PEG), oils).
55. ADVANTAGES OF NANO SUSPENSIONS
1) Applied for the poorly water soluble drugs.
2) Improved biological performance
3) Ease of manufacture & scale-up
4) Long-term physical stability
5) Rapid bioavailability in the oral administration
56. PREPARATION OF NANO SUSPENSIONS
Two techniques are used for the preparation of Nano suspensions which
a. Bottom-up technique by;
I. Micro precipitation,
II. Micro emulsion
b. Top- down technique by;
I. High pressure homogenization,
II. Wet milling method
57. 4) NANOEMULSIONS
Nano emulsions may be defined as oil-in-water (o/w), water- in-oil (w/o)
emulsions with mean droplet diameters ranging from 50 to 1000nm.
Usually, the average droplet size is between 100 & 500 nm.
The particles can exist as water-in-oil & oil-in-water forms, where the core of
particle is either water or oil, respectively.
Do not show the problems of inherent creaming, flocculation, coalescence, & sedimentation,
which are commonly associated with macro emulsions.
These can be formulated in variety of formulations such as foams, creams, liquids, & sprays.
These are non-toxic & non-irritant, hence can be easily applied to skin & mucous membranes
Reduction of globules as the potential to
-Increase surface area
-Increase oral bioavailability
59. Nano emulsions are prepared by three methods:
a. High-pressure homogenization
b. Micro fluidization
c. Phase inversion method.
60. 5) LIPOSOMES
Liposomes are simple microscopic vesicles in which an aqueous volume is entirely enclosed by a
Phospholipids bilayer molecule.
The size of a liposome ranges from some 20 nm up to several micrometres.
Based on size & no. of bilayer:
1. Small unilamellar vesicles [ SUV ]
2. Large unilamellar vesicles [ LUV ]
3. Multilamellar vesicles [ MLV ]
The name comes from Greek Word
“Dendron” which means “TREE”.
They are family of Nano sized ,highly
branched three dimensional molecules.
The first & most widely studied dendrimers
are polyamidoamine ( (PAMAM) dendrimer.
They consist of three major architectural components:
2. Branching Unit
3. End groups
64. 7) NANOSHELLS COATED WITHGOLD
This is type of spherical nanoparticle consisting of dielectric core which is covered by a thin
In cancer applications, antibodies or other biomolecules are attached to the gold surface to
target at tumor site.
-Dielectric core ( gold sulfide or silica)
-Metal shell (gold)
65. Particle < 75nm diameter absorb & others scatter the incidence light.
Nano shells strongly absorb infrared light while normal tissue is transparent to
Nano shell-antibody complex binds only to cancer cells.
Infrared laser heats up the Nano shells and thus cancer cells are destroyed.
Destroy breast cancer cells
66. 8) CARBONNANOTUBES
Carbon nanotubes are hexagonal networks of
1nm in diameter & 1-100nm in length.
Two types of nanotubes are present
1) single-walled nanotubes
2) multi-walled nanotubes
The advantages of nanotubes are ultra-light weight, high mechanical strength, & high
Due to their size & shape, carbon nanotubes can enter living cells without causing cell
death or obvious damage.
Carbon nanotubes have the ability to transport drug molecules, protein & nucleotides.
68. 9) QUANTUMDOTS
Quantum dots (QDs) are semiconducting nanomaterials consisting
of a semiconductor core (Cadmium selenide), coated by a shell
These are used as diagnostic tools, detection & analysis of
biomolecules, immunoassays, DNA hybridization, & transport
vehicles for DNA, protein, drugs or cells.
69. - Gene delivery
- Drug delivery
- Bio sensing
- Stem cell tracking
- Cancer studies
70. 10) NANOGELS
Nano gels are cross-linked nanoscale particles made of flexible hydrophilic polymers.
These are soluble in water.
Nano gels possess large surface area.
These are used to incorporate drugs, DNA/RNA & inorganic molecules .
These are also used for pH dependent release.
72. CHARACTERIZATION &EVALUATION OF NANOPARTICLES :
1. Particle size :
Photon correlation spectroscopy(PCS) : For smaller particle.
Laser diffractrometry : For larger particle.
Electron microscopy (EM)
Transmission electron microscopy (TEM) : Easier method & Permits differentiation among Nano
capsule & nanoparticle .
Atomic force microscope
Laser force microscope
Scanning electron microscope
Dynamic light scattering (For Nano suspension) 72
73. 2.Density :
Helium or air using a gas pycnometer
Density gradient centrifugation
3. Molecular weight :
Gel permeation chromatography using refractive index detector.
4. Structure & Crystallinity :
X-ray diffraction Thermoanalytical method such as,
1) Differential scanning calorimetry
2) Differential thermal analysis
5. Surface charge:
Surface charge of particle can be determined by
measuring particle velocity in electrical field.
-Laser Doppler velocimetry
USP TYPE 2
IMMERSED IN 900 ML
WITHDRAWN 5 ML
SOLUTION FROM THE
SPECIFIC TIME PERIODS
SAME VOLUME OF
DISSOLUTION MEDIUM IS
REPLCED IN THE FLASK
MAINTAIN THE CONSTANT
ANALYSED USING UV
77. STABILITY OF NANOPARTICLES
STABILTY CHAMBER FOR
FOR 90 DAYS
0,1,2 and 3 month time
The main goal of this presentation is to describe the nanoparticles, method of preparations,types and
characterization of nanoparticles .
The drug loaded nanospheres or Nano capsules now can be produced by simple, safe and reproducible
The limitation is one particular process is not suitable for all drugs.
Despite these technological challenges ,nanoparticles have been showing great promise for the
TARGETED AND CONTROLLED DRUG DELIVERY by S.P
. VYAS and R.K. KHAR