Nanoparticles

1. NANOPARTICLES
DR.MANISH KUMAR
MM.COLLEGE OF PHARMACY, MULLANA
AMBALA

2. MAIN FOCUSING POINT OF PRESENTATION
• INTRODUCTION
• PROPERTIES OF NANOPARTICLES
• ADVANTAGES
• DISADVANTAGES
• TYPES OF NANOPARTICLES
• PREPARATION TECHNIQUES
• EVALUATION OF NANOPARTICLES
• APPLICATION OF NANOPARTICLES
• REFERENCE

3. INTRODUCTION
The prefix nano comes from the ancient Greek word
,nanus which means very small .
DEFINATION :-
Nanoparticles are defined as 10-1000nm sized ,solid
colloidal particles that comprise of macromolecular
materials in which the active ingredient (drug or
biologically active material ) is dissolved ,entrapped,
encapsulated, absorbed,and or attached to
nanoparticle matrix .
They are composed of synthetic and semi synthetic
polymer carrying drugs or proteineous substances like
antigen .

4. NEED OF NANOPARTICLES
LIMITATIONS WITH
CONVENTIONAL DOSAGE
FORM
REQUIREMENTS
1.POOR DISTRIBUTION
2.LACK OF SELECTIVITY
3.LIMITED EFFECTIVENESS
1.CONTROLLED DRUG
DELIVERY
2.PROTECTION OF DRUG
FROM RAPID DEGRADATION

5. CLASSIFICATION OF NANOPARTICLES :-
NANOSPHERES :- Have a matrix type structure in which
the drug is dispersed.
NANOCAPSULES :- Have a system in which the drug is
confined to a cavity surrounded by unique polymer
membrane.

6. PROPERTIES OF NANOPARTICLES
SHOULD BE STABLE IN THE
BLOOD
BIODEGRADABLE
NON
INFLAMMATORY
NON
IMMUNOGENIC
NONTOXIC

7. ADVANTAGES
• INCREASED BIOAVAILABILITY .
• DUE TO SMALL SIZE CAN EASILY PENETRATE THE MAXIMUM BARRIERS.
• GOOD PROTECTION OF THE ENCAPSULATED DRUG.
• INCREASED THERAPEUTIC EFFICACY .
• RETENTION OF DRUG AT ACTIVE SITE .
• SMALL SIZED NANOPARTICLES CAN ENTER THE SMALLER CAPPILARRIES
TO ALLOW EFFICIENT DRUG ACCUMULATION AT TARGET SITES .
• ADMINISTRATRION CAN BE THROUGH VARIOUS ROUTES LIKE
ORAL,NASAL,PARENTRAL,INTRAOCULAR.
• LIPOSOMES AND POLYMER BASED NANOPARTICLES ARE
BIODEGRADABLE THEREFORE ARE POSSIBLY RISK FREE AS DO NOT
ACCUMULATE IN THE BODY .
• LESS AMOUNT OF DOSE REQUIRED.

8. DISADVANTAGES
• LIMITED DRUG LOADING ABILITIES DUE TO SMALL
SIZE.
• DISCONTINUATION OF THERAPY IS NOT POSSIBLE .
• TOXIC METABOLITES MAY FORM .
• Nanoparticles may alter physical properties and cause
particle – particle aggregation thus causing difficulty
in physical handling of nanoparticles in liquid and dry
forms due to small size .
• SMALL PARTICLE SIZE IS ALSO RESPONSIBLE FOR
BURST RELEASE .

9. TYPES OF NANOPARTICLE USED
TYPES OF NANOPARTICLE MATERIAL USED APPLICATION
1. NANOSUSPENSIONS AND
NANOCRYSTALS .
IN THIS DRUG POWDER IS
DISPERSE IN SURFACTANT
SOLUTION.
STABLE SYSTEM FOR
CONTROLLED DELIVERY OF
POORLY SOLUBLE DRUG.
2. SOLID LIPID
NANOPARTICLES.
MELTED LIPID DISPERSED IN
AQUEOUS SURFACTANT .
LEAST TOXIC AND MORE
STABLE .
3. POLYMERIC
NANOPARTICLES.
BIODEGRADABLE POLYMER. CONTROLLED AND
TARGETES DRUG DELIVERY .
4. POLYMERIC MICELLES . AMPHIPHILIC BLOCK
COPOLYMER.
CONTROLLED ANS SYSTEMIC
DELIVERY OF WATER
INSOLUBLE DRUGS.
5. MAGNETIC
NANOPARTICLES.
MAGNETITE Fe203, MEGHE
MITE COATED WITH
DEXTRAN
DRUG TARGETTING
DIAGNOSTICS TO IN
MEDICINE .
6. CARBON NANOTUBES. METALS , SEMICONDUCTORS GENE AND DNA DELIVERY .

10. POLYMER USED IN NANOPARTICLES
FORMATION
1. NATURAL POLYMERS -
#Proteins eg :- gelatin , albumin.
#Polysacharides eg :- alginates ,dextran ,chitosan .
2. SYNTHETIC POLYMERS-
#Pre-polymerized polymers eg- polystyrene .
#Poly (e-caprolactone) (PECL)
3. SEMI-SYNTHETIC POLYMER –
#Cellulose derivates – ethyl cellulose ,methyl
cellulose , cellulose acetate , cellulose nitrate.

11. TECHNIQUES OF PREPARATION
Super critical
fluid
1. Rapid
expansion
super critical
fluid .
2. Super critical
antisolvent
Preformed
polymer
1.Solvent
evaporation
method .
2.Salting out
method
Polymerization
1.Dispersion
polymerization
.
2.Emulsion
polymerization.

12. PREPARATION OF NANOPARTICLES :-
1. BY POLYMERATION METHOD :- Two approaches for
preparation
1. DISPERSION POLYMERIZATION
The methyl methacrylate monomer is dissolved in aqueous
phase .
Polymerization by chemical initiation combined with heating to
temperature above 65 c.
The oligomer formed subsequently aggregate & above certain
molecular weight precipitate in the form of nanoparticles.
Used for preparation of biodegradable polyacrylamide
& polymethyl methacrylate (PMMA) .

13. 2. EMULSION POLYMERATION :
Monomer
Dissolved in aqueous phase which contains an initiator
which is surfactant .
Vigorous agitation.
Emulsion formation .
Particle smaller than 100nm .
INITIATOR :- which generates either radicals or ions
depending upon the type of initiator & the radicals or ions
nucleate the monomeric unit & starts polymerization process.

14. 2. BY PREFORMED POLYMER METHOD
1. SOLVENT EMULSIFICATION EVAPORATION -
In this method ,preformed polymer and the drug are
dissolved in a water –immiscible organic solvent .
Mixture is emulsified in an aqueous solution having a
stabiliser to obtain ow emulsion.
For the reduction of globule size , this emulsion is exposed to
a high energy source like ( ultrasonic
sonicator,homogenisers,colloid mills etc .
After that organic solvent is removed by exposing the
solution to heat and vaccum ,thus fine aqueous dispersion of
nanoparticles is formed.

15. 2. SALTING OUT METHOD –
In this method , a water miscible solvent is
separated from aqueous solutions through a salting
out effect . (ACETONE IS PREFERRED AS WATER
MISCIBLE SOLVENT )
PROCEDURE :- Preformed polymer + drug = dissolved in acetone .
obtained mixture (ow) is emulsified under magnetic stirring in an
aqueous gel having the salting out agent (electrolytes eg- magnesium
acetate or magnesium chloride ) and colloidal stabiliser .
Further resultant emulsion is diluted with a sufficient volume of water
to increase the diffusion of acetone into aqueous phase.
This increases the formation of nanoparticles. Thereafter the solvent
and salting out agent are eliminated by cross –flow filtration .

16. 3. SUPER CRITICAL FLUID TECHNOLOGY(SCF):-
1. RAPID EXPANSION OF SUPERCRITICAL SOLUTION :- ( For drug
soluble in SCF)
DRUG DISSOLVED IN SUPER CRITICAL FLUID .
SOLUTION SPRAYED INTO REGION OF LOW PRESSURE.
SOLVENT POWER OF SUPER CRITICAL FLUID DECREASES.
PRECEPITATION OF NANOPARTICLES.
RAPID EXPANSION
OF SUPERCRITICAL
SLUTION (RESS).
SUPER CRITICAL ANTI-
SOLVENT (SCA)

17. 2. SUPER CRITICAL ANTI- SOLVENT ( SCA) :- For those drugs which are insoluble in SCF
ADVANTAGES OF SCF METHOD :-
1. Helps in formation of dry nanoparticles.
2. Involves use of environment friendly solvent like super critical carbon
dioxide or nitrogen .
3. Contain very low traces of organic solvent .
DRUG + METHANOL DRUG IS DISSOLVED
ADD SUPER
CRITICAL FLUID
(miscible with
methanol)
PRECEPITATION OF
DRUG AS FINE
PARTICLES

18. EVALUATION PARAMETER OF
NANOPARTICLES
1. – YIELD OF NANOPARTICLES :-
percentage yield =
𝑎𝑐𝑡𝑢𝑎𝑙 𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑝𝑟𝑜𝑑𝑢𝑐𝑡
𝑡𝑜𝑡𝑎𝑙 𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑒𝑥𝑖𝑐𝑖𝑝𝑖𝑒𝑛𝑡 𝑎𝑛𝑑 𝑑𝑟𝑢𝑔
2. – DRUG CONTENTSURFACE ENTRAPMENT DRUG ENTRAPMENT :-
percentage drug entrapment =
𝑚𝑎𝑠𝑠 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑖𝑛 𝑛𝑎𝑛𝑜𝑝𝑎𝑟𝑡𝑖𝑐𝑙𝑒
𝑚𝑎𝑠𝑠 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑢𝑠𝑒𝑑 𝑖𝑛 𝑓𝑜𝑟𝑚𝑢𝑙𝑎𝑡𝑖𝑜𝑛
×100
3. – PARTICLE SIZE :-
Particle size and its distribution is important characteristics in nanoparticles as they plays
major role in distribution , pharmacological activity , toxicity and target to specific sites.
Advance methods to determine the particle size of nanoparticles is by :-
# PHOTON –CORRELATION SPECTROSCOPY .
( used for smaller particle )
# SCANNING ELECTRON MICROSCOPY .
( for high resolution )

19. 4. PARTICLE SHAPE :- Particle shape of the nanoparticles suspensions is determined by
scanning electron microscopy (SEM) . In order to form the solid particles these
nanosuspension were subjected to lyophilisation .
5. ZETA POTENTIALSURFACE CHARGE :- Zeta potential is the potential difference existing
between the surface of a solid particle immersed in a conducting liquid and the bulk of the
liquid . The surface charge of the nanoparticle is usually measured by zeta potential.
.

20. 6. ATOMIC FORCE MICROSCOPY (AFM) :- It offers a ultra high
resolution in particle size measurement and is based on
physical scanning of sample at sub micron level using a probe
tip of atomic scale . AFM provides the most accurate
description of size and size distribution. AFM is used to make
3D images at high levels of magnification down to few
nanometers.

21. 7. INVITRO DRUG RELEASE STUDIES
A. DISSOLUTION ;-
USP TYPE 2
RPM 50
IMMERSED IN 900 ML OF
PHOSPATE BUFFER
SOLUTION
TEMPERATURE
MAINTAINED AT 37
degree CELSIUS
WITHDRWAN 5ML
SOLUTION FROM THE
MEDIUM
SPECIFIC TIME PERIODS
SAME VOLUME OF
DISSOLUTION MEDIUM
REPLACED IN THE FLASK
MAINTAIN THE
CONSTANT VOLUME
WITHDRAWN SAMPLES
ANALYSED USING UV
SPECTROPHOTOMETERY

22. B. DIFFUSION CELL :-
APPARATUS CONSISTS OF TWO CHAMBERS
SEPARATED BY MEANS OF HYDROPHILLIC MILLIPORE
MEMBRANE WITH LOW PROTEIN BINDING
THE DIIFUSION CELL IS PLACED ON A SHAKER STAND
NANOPARTICLES SUSPENSION IS FILLED IN THE DONAR
COMPARTMENT AND PHOSPHATE BUFFER IN RECEPTOR
COMPARTMENT
ALIQUOTS OF PH BUFFER ARE PERIODICALLY REMOVED FROM
THE RECEPTOR CHAMBER ANS IS ASSAYED

24. APPLICATIONS OF NANOPARTICLES
• Used in targeted drug delivery in brain therapy, used for delivery of proteins and
peptides.
• Used in targeting of nanoparticles to epithelial in the GI tract using ligands .
• Nanoparticles for gene delivery .
• Used in bio detection of pathogens .
• Used in Stem cell therapy, cancer therapy .
• Helps to deliver drugs across the blood brain barrier ,also used to formulate
sustained release preparations.
• Nanoparticles helps to improve the solubility and bioavailability of poorly soluble
drugs .
• Used to in ocular drug delivery and for delivering pilocarpine and miotic drugs .
• Solid lipid particles (SLN) are used to formulate skin and hair care products in which
the oily core contains different cosmetic oils and lipophilic agents .

25. COMMERICAL PRODUCTS OF
NANOPARTICLES
COMPANY TRADE NAME COMPOSITIO
N
INDICATION ROUTE
NOVAVAX ESTASORB MICELLULAR
ESTRADIOL
MENOPAUSAL
THERAPY
TOPICAL
GENZYME RENAGEL POLY
(ALLYLAMINE
HYDROCHLOR
IDE)
END STAGE
RENAL
DISEASE
ORAL
BERNA
BIOTECH
EPAXAL LIPOSOMAL
IRIV VACCINE
HEPATITIS A IM
ELAN , ABOTT TRICOR NANOCRYSTA
LLINE
FENOFIBRATE
ANTI
HYPERLIPIDE
MIC
ORAL
BIO SANTE ELESTRIN ESTRADIOL
GEL
MENOPAUSAL
WOMEN
TRANSDERMA
L

26. REFERENCES
• N.K .JAIN CONTROLLED AND NOVEL DRUG DELIVERY ,
CBS PUBLISHERS AND DISTRIBUTION ,NEW DELHI
FIRST EDITION 1997.
• www.slideshare.com
• Images are from google .
• Vyas S.P and Khar R.K., controlled drug delivery ,
vallabh prakashan.

27. THANK
YOU