1. GANDHI SONAM M.
1ST M.PHARM
INDUSTRIAL PHARMACY
SUBJECT TEACHER :
MR.SATEESHA S.B

2. What is Nanotechnology?
 Nanotechnology is the act of purposefully
manipulating matter at the atomic scale,
otherwise known as the "nanoscale."
 In Pharmacy its all about synthesizing,
characterizing and screening the particle at
Nano range.

4. Therapeutic
Introduction application of
Nanoparticles
Various methods Surface engineering
of preparation of Nanoparticles
In Vivo fate and
Pharmaceutical Biodistribution of
aspects of Nanoparticles
Nanoparticles
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5. Introduction
Targeted drug delivery implies for selective and effective
localization of pharmacologically active moiety at
preidentified targets in therapeutic concentration, while
restricting its access to non-target normal cellular linings,
thus minimizing toxic effects and maximizing therapeutic
index
The colloidal carriers based on biodegradable and
biocompatible polymeric systems like liposomes,
nanoparticles and micro emulsion have largely influenced
the controlled and targeted drug delivery concepts

6. Nanoparticle
dimensions between 1 nm and 1000 nm
Nano derives from the Greek word "nanos",
which means dwarf or extremely small. It can be
used as a prefix for any unit to mean a billionth
of that unit.
A nanometer is a billionth of a meter or
10-9 m.
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7.  Nanoparticles are solid colloidal particles
ranging from 1 to 1000 nm in size, they consist
of macromolecular materials in which the
active ingredients (drug or biologically active
material) is dissolved, entrapped, or
encapsulated, or adsorbed.
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8. Definition
Nanocapsules: in which the drug is
confined to an aqueous or oily core
surrounded by a shell-like wall.
Alternatively, the drug can be covalently
attached to the surface or into the matrix

9. Nanoparticles
Nanospheres Nanocapsules
Matrix type Membrane wall
structure in structure with an
which a drug is oil core containing
dispersed drug
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12. ADVANTAGES:
 Nanoparticle drug carriers have higher stabilities
 Nanoparticles have higher carrier capacity
 Feasibility of incorporation of both hydrophilic and
hydrophobic substances
 Feasibility of variable routes of administration
 Nanoparticles are biodegradable, non-toxic and capable
of being stored for longer periods.
 nanoparticles can also be used for controlled delivery of
drugs
 Nanoparticles reduces dosing frequency and have higher

13. Disadvantages of nanoparticles
Polymeric nanoparticles posses limited drug-loading
capacity
On repeated administration, toxic metabolites may be
formed during the biotransformation of polymeric carriers.
The polymeric nanoparticles are relatively slowly
biodegradable which might cause systemic toxicity.

14. 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)

15. Preparation of nanoparticles:
Nanoparticle Preparation Using Polymerization
Based Methods
 The polymers used in this are poly methyl
methacrylate, polyacrylamide, polybutyl
cyanoacrylate.,etc
Two approaches adopted for preparation of
nanoparticles using polymerization technique are
1. Methods in which the monomer to be polymerized is
emulsified in a non-solvent phase(emulsion
polymerization)
2. Methods in which the monomer is dissolved in a
solvent for the resulting polymer (dispersion
polymerization)

16. Methods used for nanoparticle preparation
Methods used for nanoparticle preparation
are
1. Emulsion polymerization
2. Dispersion polymerization
3. Interfacial polymerization
4. Interfacial complexation

17. 1. EMULSION POLYMERIZATION:
The process can be
 Conventional – continuous phase is
aqueous i.e., o/w emulsion
 Inverse – continuous phase is organic i.e.,
w/o emulsion.
Two mechanisms of emulsion polymerization
are
A. Micellar nucleation and polymerization
B. Homogenous nucleation and
polymerization

18. A. Micellar nucleation and polymerization
 In this the monomer is emulsified in non-solvent
phase using surfactant molecules
This leads to the formation of
i. Monomer- swollen micelle
ii. Stabilized monomer droplet
• Monomer swollen micelle have sizes in
nanometric range and have much larger
surface area compared to monomer droplet
• Polymerization reaction proceeds through
nucleation and propagation stage in presence
of chemical or physical initiator.

19. CONTINUE……
 Energy provided by initiator creates free
monomers in continuous phase, which then collide
with surrounding unrelative monomers and initiate
polymerization chain reaction.
 The monomer molecule reaches the micelle by
diffusion from the monomer droplets through
continuous phase, thus allowing polymerization to
progress within micelles. Here monomer droplets
act as reservoirs of monomers.

20. Surfactant Monomer
droplet
Drug
Monomer
Monomer supply
Monomer supply for growth
Catalyst
Monomer bearing Stabilized polymeric
micelle Nucleated micelle nanospheres
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21. B. Homogenous nucleation and polymerization
 In this method monomer is sufficiently
soluble in continuous outer phase.
Nucleation and polymerization can
directly occur in this phase leading to
formation of primary chains called
oligomers.
 In this both micelle and droplets act as
monomers reservoir throughout
polymer chain length. When oligomers
reach certain length, they precipitate
and form primary particles and
stabilized by surfactant molecules
provided by micelle and droplets in
which the drug will entrapped to form
nanoparticles.

22. Surfactant
Drug
Monomer
Monomer
droplet
Activated Monomer Oligomer Primary Stabilized polymeric
particle nanospheres
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23. .
DISPERSION POLYMERIZATION
 In emulsion polymerization, monomer is emulsified
in non-solvent phase by means of surfactants. In
case of dispersion polymerization, monomer is
dissolved on aqueous medium.
 The nucleation is directly induced in aqueous
monomer solution and presence of stabilizer or
surfactant is not necessary for formulation of
stable nanospheres.

24. CONTINUE………
 This method is used to prepare biodegradable
polyacrylamide and polymethyl-methacrylate
(PMMA) nanoparticles.
 Being very slowly biodegradable and
biocompatible, PMMA nanoparticles have
been considered as optimal polymeric
systems for vaccination purpose.

25. 3. INTERFACIAL POLYMERIZATION
 In this method, a polymer that becomes core of nano-
particle and drug molecule to be loaded is dissolved in
volatile solvent.
 Solution is then placed in to a non-solvent for both
polymer and core phase
 Polymer phase is separated at o/w interphase. Resultant
mixture instantly turns to milky owing to formulation
of nanocapsules.

26. PREPARATION OF NANOPARTICLES BY
INTERFACIAL POLYMERIZATION :
Core phase + drug Polymer phase
Core dispersed in polymer phase
-- - - - - - - - - - -
-- - - - - - - - - - - (O/W emulsion)
Non-solvent, which
precipitate out polymer from
either of phases
Nanocapsules
( 30-300 nm )
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27. CONTINUE………
 Size of nanocapsules is 30-300 nm
 Drug loading depends on drug solubility
in core phase
 Surfactant can be added to stabilize
dispersion.
 Example: encapsulation of proteins,
enzymes, antibiotics.etc.,

28. PHARMACEUTICAL ASPECTS OF
NANOPARTICLES:
 From pharmaceutical point of view
nanoparticles prepared should be free from
toxic impurities, should be easy to store
and administer and should be sterile if
parenterally used.
Three parameters performed before
releasing them for clinical trials are
 Purification
 Freeze drying
 Sterilization

29. Purification of nanoparticles
Commonly used methods are
 Gel filtration
 Dialysis
 Ultra-centrifugation
 Cross flow filtration
A new cross – flow filtration method is used for
purification of nanoparticles in industrial point of
view. In this method nanoparticle suspension is
filtered through membranes, with the direction of fluid
being tangential to the surface of the membrane. As
a result clogging of filters is avoided.

30.  CONTINUE……..
 The suspension is subjected to several filtration
cycles, while the filtrate is discarded containing
soluble impurities.
 This leads to the concentration of suspension.
After this, water is added to maintain the
volume of circulation constant.
 This is a simple and can be done at a faster
rate.
 Purification of large amounts of nanoparticles
can be done without alteration in the sizes.

31. Cross-flow filtration technique:
Nanopraticles
Impurites
Membrane
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32. Gel filtration :
Remark :
Nanoparticle
High molecular weight
substances and impurities
Impurity are difficult to remove
Schematic principle
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34. Dialysis :
Remark :
• High molecular weight
impurities are difficult to
remove
•Time consuming process
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35. Freeze drying of nanoparticles:
 This involves freezing of the nanoparticles and subsequent
sublimation of its water content under reduced pressure to get a
free flowing powdered material.
 Advantages:
 Prevention from degradation and solubilization of polymer.
 Prevention from drug leakage, drug desorption .
 Easy to handle and store and helps in long term preservation.
 Readily dispersed in water without modifications in their
physicochemical properties.
 Prevention from drug leakage
Disadvantage:
 Nanocapsules having an oily core surrounded by polymer wall
tend to agglomerate.
 This can be overcome by dessicating in lyoprotective agent ex:

36. Sterilization of nanoparticles:
 Nanoparticles intended for parenteral use should be
sterilized to be pyrogen free before using on animals
or humans.
 Sterilization is achieved by using aseptic technique
throughout preparation, processing and formulation
or by autoclaving or using γ- irradiation.
 Autoclaving and γ- irradiation show impact on the
physicochemical properties of the particles with
modification of particle size stability and drug release
characteristics.
 Sterilization is a critical step and should be
systematically investigated during formulation
development stage.

37. Characterization of nanoparticles:
1. Size and morphology
2. Specific surface
3. Surface charge and electrophoretic
mobility
4. Surface hydrophobicity
5. Density

38. Size and
morphology:
Methods used are
 Photon correlation spectroscopy(PCS)
 Laser defractometry
 Transmission electron microscopy(TEM)
 Scanning electron microscopy(SEM)
 Atomic force microscopy
 Mercury porositometry
 Freeze fracture

39.  PCS and EM are widely used to
determine the particle size. Better
results are obtained using freeze
fracture and photon correlation
spectroscopy.
 Freeze fracture microscopy: In this poly
(methyl methacrylate) is used. Only few
particles are analyzed. This method also
gives morphology of inner structure of
particles.

40. CONTINUE….
 Scanning electron microscopy: This
measures individual particles. It is a less time
taking process.
 Atomic force microcopy images can be
obtained in an aqueous medium so this is an
effective technique to investigate nanoparticle
behavior in biological environment.

41. Scanning Electron Microscopy
Field
Emission
SEM
Transmission Electron Microscopy Atomic Force Microscopy

42. 2. Specific surface: the specific surface area of
freeze dried nanoparticles is measured using
sorptometer. The residual surfactant reduces
the specific surface area.
3. Surface charge and electrophoretic mobility:
the nature and intensity of the surface charge
of nanoparticles is very important as it
determines their interaction with the biological
environment. Surface charge measured using
laser Doppler anemometry or velocimetry.
Surface charge is also measured using
electrophoretic mobility in phosphate saline
buffer (7.4) and human serum.

43. 4. Surface hydrophobicity: the hydrophobicity
determines the fate of nanoparticles and
their contents. The measurement of angle
of contact suggests about the hydrophilicity
and hydrophobicity of the nanoparticles.
Recently X-ray photoelectron spectroscopy
is used to identify chemical groups on
surface of nanoparticles.
5. Density: the density of nanoparticles is
determined with helium or air using a gas
Pycnometer.

44. In vitro release profile of
Drugs
•Using standard dialysis or diffusion cell.
•Double chamber diffusion cell on shaker stand.
•The donor chamber is filled with nanoparticulate
suspension.
•Receptor chamber with plain buffer.
•The receptor chamber is assayed at different time
intervals using standard procedure.

45. In vivo fate and biodistribution of
Nanoparticles
RES
nanoparticles Opsonin
adsorption Phagocytosis
recognition
opsonins adsorb on to the surface of colloidal carriers
and render particles recognizable to the “RES” thus they
mediate their endocytosis by fixed macrophages of “RES”
and circulating monocytes

47. Surface engineering of
Nanoparticles
Nanoparticles are surface engineered for various purposes.
They are classified as
Magnetically guided nanoparticles
Bioadhesive guided nanoparticles
Antibody guided nanoparticles

48. Magnetically guided
Nanoparticle
Magnets can be used to deliver forces and energy, and
can be sensed remotely
Magnetic nanoparticles can be used both in vivo and
in vitro, to great effect
Endomagnetics has real promise for oncology,
hematology, drug delivery, stem cell therapies

49. Nanoparticles are rendered magnetic by incorporating iron
particles (10-20nm) simultaneously with the drug during the
preparation stage; the magnetic nanoparticles are then injected
through the artery, supplying the tumour tissue and guided
externally

50. Nanoparticles coated
with Antibodies
Target specific antibodies to the nanoparticle surface
may facilitate their delivery to specific sites. Monoclonal
antibodies can be fixed on nanoparticles by direct
adsorption or via a spacer molecule or by covalent
linkage,
Tumour specific monoclonal antibodies conjugated
to super-paramagnetic monocrystalline iron oxide
nanoparticles (MION) could be used to yield specific
diagnoses with the use of MR imaging

51. Nanoparticles for
Bioadhesion
Here the drug adhere to the mucosal surface
and provide better opportunity for drug
absorption in a controlled manner, the fate of
nanoparticles follows three different pathways:
1) Bioadhesion,
2) translocation through the mucosa and
3) transit and direct fecal elimination

52. APPLICATIONS
Application Purpose
Cancer therapy Targeting and enhanced uptake of
antitumor agents
Intracellular targeting Target intracellular infections
Prolonged systemic circulation To prolong the drug effect
Vaccine adjuvant Enhances immune response
Peroral absorption Enhanced bioavailability
Ocular delivery Improved retention of drug and
reduced washout
Other applications Crosses blood-brain barrier
Improved absorption
Oral delivery of peptides.

53. Parenteral Administration
 Delivery of anticancer drugs
 Nanoparticles have been found to
accumulate in tumors after IV
administration
 Reduction in toxicity of anticancer drugs
as drugs are concentrated mainly in liver
and spleen
 Useful in treatment of hepatic
metastases

54.  Material :
poly (alkylcyanoacrylate) nanoparticles with
steroids, anti-inflammatory agents, anti
bacterial agents for glaucoma
 Purpose :
improved retention of drug / reduced wash
out.
74

55. Viral infections
 Nanoparticles represent an interesting for
selective transport of antiviral agents displaying
poor selectivity and/or short plasma half-life.
 For ex: nanoparticles loaded with protease
inhibitor sesquinvir was shown to be effective in
HIV infected human macrophage cultures

56.  Material :
poly ( methylmethacrylate ) nanoparticles with
vaccines ( oral and intramuscular
immunization )
 Purpose :
enhances immune response, alternate
acceptable adjuvant
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57.  Material :
Polyesters with adsorbed polyethylene glycols
or pluronics or derivatized polyesters
 Purpose :
Prolong systemic drug effect, avoid uptake by
the reticuloendothelial system
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58. Various forms of nanoparticle
systems

59. COMMERCIAL PRODUCTS

60. Conclusion
Polymeric particulate carrier systems are expected to target
the inflamed tissue
This new delivery system allows the desired drug to
accumulate In the inflamed tissue with high efficiency.
The drug is concentrated at its site of action, which
reduces possible adverse effects and enhances the effect
of the administered dose
The sustained drug release allows pharmacological effects
to be extended due to the prolonged presence time of the
carrier system at the targeted inflamed area.

61. References
Vyas and Khar.Targeted and Controlled Drug
Delivery Novel Carrier Systems.First
edition,CBS Publishers, New Delhi.
healthcare by sensing, moving and heating
magnetic nanoparticles in the human body. Quentin
Pankhurst, Deputy Director: London Centre for
Nanotechnology
http://jpet.aspetjournals.org

62. REFERENCES
 Gilbert s Banker. Modern Pharmaceutics. 4 th
edition.
 N.K. Jain. Controlled and Novel drug delivery.
1 st edition.
 Y.W. Chien. Novel Drug Delivery Systems.
 Binghe Wany, Teruna Siahaan, Richard A
Soltao. Drug Delivery Principles and
Applications.
 Krishna RSM, Shivakumar HG, Gowda DV
and Benerjee S. Nanoparticles: A Novel
colloidal drug delivery system. Ind J Pharm
Ed Res.2006; 40(1):15-9.