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1. NANOPARTICLES
Ravish Yadav

2. Definition:
“ Nanoparticles are sub-nanosized colloidal structures
composed of synthetic or semi-synthetic polymers.”
Size range : 10–1000 nm
The drug is dissolved, entrapped, encapsulated or attached
to a nanoparticle matrix.
Based On Method Of Preparation:
Nanocapsules:- Nanocapsules are systems in which the
drug is confined to a cavity surrounded by a unique polymer
membrane.
Nanospheres:- Nanospheres are matrix systems in which
the drug is physically and uniformly dispersed.

3. Nanoparticulate drug-delivery systems

4. Classification Of Nanoparticles:
Solid Lipid Nanoparticles
Polymeric Nanoparticles
Ceramic Nanoparticles
Hydrogel Nanoparticles
Copolymerized Peptide Nanoparticles
Nanocrystals and Nanosuspensions
Nanotubes And Nanowires
Functionalized Nanocarriers
Nanospheres
Nanocapsules

5.  Solid Lipid Nanoparticles:
•New type of colloidal drug carrier system for i.v.
•Consists of spherical solid lipid particles in the nm range,
dispersed in water or in aqueous surfactant solution.
Polymeric nanoparticles (PNPs) are defined as particulate dispersions
or solid particles with size in the range of 10-1000nm.
•Composed of synthetic or semi-synthetic Polymers.
Biodegradable polymeric nanoparticles Polylactic acid (PLA),
polyglycolic acid (PGA), Polylactic - glycolic acid (PLGA), and
Polymethyl methacrylate (PMMA) Phospholipids
Hydrophobic core

6. Ceramic Nanoparticles:
•These are the nanoparticles made up of inorganic (ceramic)
compounds silica, ( Inorganic/metal) titania and alumina.
Exist in size less than 50 nm, which helps them in evading
deeper parts of the body.
Hydrogel nanoparticles:
• Polymeric system involving the self-assembly and self
aggregation of natural polymer amphiphiles cholesteroyl
pullulan , cholesteroyl dextran and agarose cholesterol
groups provide cross linking points.

7. Copolymerized Peptide Nanoparticles:
•Drug moiety is covalently bound to the carrier instead of
being physically entrapped.
Nanocrystals And Nanosuspensions: Pure drug coated
with surfactant, Aggregation of these particles in crystalline
form .Drug powder dispersed in aqueous surfactant
solution.
Functionalized Nanocarriers
•Biological materials like proteins, enzymes, peptides etc…
are being utilized as a carriers for the drug delivery.

8. Advantages Of Nanoparticles:
• Nano particle can be administered by parenteral, oral,
nasal,occular routes.
• By attaching specific ligands on to their surfaces,nano particles
can be used for directing the drugs to specific target cells.
• Improves stability and therapeutics index and reduce toxic
affects.
• Both active & passive drug targetting can be achieved by
manipulating the particel size and surface characteristics of nano
particles

9. Disadvantages Of Nanoparticles
Small size & large surface area can lead to particle
aggregation .
Physical handling of nano particles is difficult in
liquid and dry forms.
Limited drug loading.
Toxic metabolites may form.

10. Preparation of polymeric Nanoparticles
Dispersion
polymerization
(DP)
Emulsion
polymerization
(EP) Solvent
evaporation
method
Solvent
Displacement
method
EP in aqueous
Continuous
phase
EP in an organic
continuous
phase
Salting out
tech.
Polymerization Preformed
polymer
Super critical
fluid tech.

11. The selection of matrix materials is dependent on many factors including
(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;
(e) Drug release profile desired; and
(f) Antigenicity of the final product.

12. Polymers For Nanoparticles
Natural hydrophilic polymers
•Proteins: - Gelatin, albumin, lectins, legumin.
•Polysaccharides: - alginate, dextran, chitosan,
agarose.
Synthetic hydrophobic polymers
•Pre-polymerized polymers: - Poly (e-caprolactone)
(PECL),Poly (Lactic acid)(PLA), Polystyrene
•Polymerized in process polymers: - Poly (isobutyl
cyanoacrylates) (PICA), Poly (butyl cyano acrylates)

13. A. Nanoparticle Prepared By Polymerization Method
 Two approaches for preparation :
1. Dispersion polymerization (DP):
 Used for preparation of biodegradable polyacrylamide &
polymethyl methacrylate (PMMA).
 The acrylate or methyl methacrylate monomer is
dissolved in aqueous phase.
polymerization by γ-irradiation or chemical initiation
combined with heating to tem. above 65 ˚c.
The oligomer formed subsequently aggregate & above
certain molecular weight precipitate in the form of
nanoparticles

14. 2. Emulsion polymerization (EP):
Monomer
Dissolved in aqueous phase which contains an
initiator which is a surfactant
Vigorous agitation
Emulsion formation
Particle smaller than 100nm
Initiator which generates either radicals or ions depending
upon the type of initiator & these radicals or ions nucleate the
monomeric unit & starts polymerization process.

15. 2.1)EP in an organic continuous phase:-Water soluble
monomers are polymerized.
Polyalkyl cynoacrylate (PACA) nanoparticles were prepared
by EP in continuous organic phase.
Drug dissolved in aq.phase
Organic solvent (hexane,
chloroform)containing surfactant
Emulsified
Microemulsion &monomer
diffuse in swollen micelles
OH¯ ions initiate
polymerization
Nanospheres

16. Preformed polymer:-
1. Solvent evaporation method :
Drug & polymer is dissolved in organic solvent.
Emulsified with an aq. phase containing surfactant to obtain
o/w emulsion.
Organic phase is then evaporated
Nanoparticles
Example : polylactic acid nanoparticle loaded with
testosterone using poloxamer 188 as stabilizer by using
homogenizer.

17. 2. Solvent displacement / Nanoprecipitation :
Useful for slightly water soluble drug.
Drug dissolved in organic
phase(ethanol/methanol)
Aq.phase
Displacement of organic phase
Immediate polymer precipitation because
of complete miscibility of both the phase.
Nanoparticles
Emulsified

18. 3. Salting out method :
Suitable for drug & polymers that are soluble in polar
solvent such as acetone or ethanol.

19. C. Super Critical Fluid Technology (SCF) :
Advantages:
Formation of dry nanoparticles.
Rapid precipitation process.
Contain very low traces of organic solvent.
Involves use of environment friendly solvent like super
critical carbon dioxide or nitrogen.
SCF Technology
Rapid Expansion of
Supercritical solution (RESS)
Super Critical Anti-
solvent (SCA)
For drugs soluble in SCF For drug insoluble in SCF

20. Rapid expansion of supercritical solution:
• Drug dissolved in super critical fluid
• Solution sprayed into region of low pressure.
• Solvent power of super critical fluid decreases.
• Precepitation of nanoparticles

21. Super Critical Anti-solvent (SCA)
Drug + Methanol
Drug is dissolved
Add Super critical fluid
(miscible with methanol)
Precepitation of drug as fine particles

22. Equipments for Nanoparticles
• Homogenizer
• Ultra Sonicator
• Mills
• Spray Milling
• Supercritical Fluid Technology
• Electrospray
• Ultracentrifugation
• Nanofiltration

23. Homogenizer & Ultra Sonicator

24. Nano mill- Manufacturing Platform

25.  Evaluation of nanoparticles :
1. Particle size
2. Density
3. Molecular weight
4. Structure and crystallinity
5. Specific surface area
6. Surface charge & electronic mobility
7. Surface hydrophobicity
8. Invitro release
9. Nanoparticle yield
10. Drug entrapment efficiency

26. 1.Particle size :
 Photon correlation spectroscopy (PCS) : For smaller particle.
 Laser diffractrometry : For larger particle.
 Electron microscopy (EM) : Required coating of conductive material such
as gold & limited to dry sample.
 Transmission electron microscopy (TEM) : Easier method & Permits
differntiation among nanocapsule & nanoparticle.
 Atomic force microscope
 Laser force microscope Highresolution
Scanning electron microscope microscope

27. 2.Density :
 Helium or air using a gas pycnometer
 Density gradiant 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
3) Thermogravimetry

28. 5. Specific surface area :
Sorptometer
specific surface area A = 6
Density * diameter of particle
6. Surface charge & electronic mobility :
Surface charge of particle can be determined by measuring
particle velocity in electrical field.
Laser Doppler Anemometry tech. for determination of
Nanoparticles velocities.
Surface charge is also measured as electrical mobility.
Charged composition critically decides bio-distribution of
nanoparticle .
Zeta potential can also be obtain by measuring the

29. electronic mobility.
7. Surface Hydrophobicity :
Important influence on intraction of nanoparticles with biological environment.
Several methods have been used,
1. Hydrophobic interaction chromatography.
2. Two phase partition.
3. contact angle measurement.
8. Invitro release :
Diffusion cell
Recently introduce modified Ultra-filtration tech.
Media used : phosphate buffer
9. Nanoparticle yield :
% yield = Actual weight of product
Total weight of excipient & Drug

30. 10. Drug entrapment efficiency :
Drug entrapment % = Mass of drug in Nanoparticles
Mass of drug used in formulation
100

31. Applications

32. EMEND Rapamune
OLAY MOISTURIZERS
(Merck & Co. Inc) (Wyeth-Ayerst Laboratories)
(American Biosciences, Inc.)
ABRAXANE
(Proctor and Gamble)

33. Conclusion
Nanoparticles are one of the novel drug delivery systems,
which can be of potential use in controlling and targeting drug
delivery as well as in cosmetics textiles and paints. Judging by
the current interest and previous successes, nanoparticulate
drug delivery systems seems to be a viable and promising
strategy for the biopharmaceutical industry.

34. References
•Encyclopedia of controlled drug delivery system edited by
Edith Mathiowitz, Pg. no:551-564.
•Vyas S.P. , Khar R.K. Targeted & Controlled Drug Delivery,
Novel Carrier Systems, CBS Publication ,2002 ,Page No.249-
277,331-387.
•www.pharmainfo.net/reviews/nanoparticles-and-its-
applications-field-pharmacy
•Nanoparticles –A Review by VJ Mohanraj & Chen Y, Tropical
Journal of Pharmaceutical Research 2006; 5(1): 561-573
•Google.com(images)
•Jain N. K., Controlled and novel Drug Delivery, 1st edition
2001, CBS Publication; 292 - 301.