This document discusses nanoparticles as subnanosized colloidal drug delivery systems ranging from 10-1000 nm in diameter. It defines nanoparticles and describes their basic concept of selectively delivering drugs to target tissues while restricting access to non-target tissues. The document outlines ideal characteristics of nanoparticles and various methods for their preparation, characterization, and evaluation. It provides examples of nanoparticle applications such as cancer therapy, intracellular targeting, vaccines, DNA delivery, and ocular delivery. The document concludes by listing references for further information on nanoparticles.

1. Presented By
Bindiya Patel
M.PHARM
(PHARMACEUTICS)

2. 1. INTRODUCTION
2. CONCEPT
3. ADV AND DISADV
4. IDEAL CHARACTERISTICS
5. METHOD OF PREPARATION
6. CHARACTERIZATION
7. EVALUATION
8. APPLICATIONS
2

3. INTRODUCTION
» DEFINITION:
» Nanoparticles are subnanosized colloidal drug delivery systems
» particle size ranges from 10-1000 nm in diameter.
» They are composed of synthetic or
semi synthetic polymers carrying drugs or
proteinaceous substances, i.e. antigen(s).
» Drugs are entrapped in the polymer matrix particulates or
solid solutions or may be bound to particle surface by
physical adsorption or in chemical form.
3

4. » The basic Concept involved is :
» Selective and Effective Localization of pharmacologically
active moiety at preselected target(s) in therapeutic
concentration,,
» Provided restriction of it’s access to non-target normal tissues
and cells.
» Nanoparticles are mainly taken by :
Reticulo Endothelial System (RES), After the
administration; 4

5. » Hence are useful to carry drugs to the liver and to
cells that are phagocytically active.
» By modifying the surface characteristics of the
nanoparticles it is possible to enhance the delivery
of drugs to spleen relative to the liver.
» Distribution of the nanoparticles in the body may
be achieved possibly by :
» Coating of nanoparticles with certain Serum
components, Attachment of antibodies or
sulfoxide groups and the use of Magnetic
nanoparticles. 5

6. » Reduction in the frequency of the dosages
taken by the patient
» More uniform effect of the drug
» Reduction of drug Side Effects
» Reduced fluctuation in circulating drug levels
» Avoids hepatic first pass metabolism
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7. » High cost
» Productivity more difficult
» Reduced ability to adjust the dose
» Highly sophisticated technology
» Requires skills to manufacture
» Difficult to maintain stability of dosage form.
E.g.: Resealed erythrocytes stored at 40C.
7

8. » It should be biochemical inert , non toxic and
non-immunogenic.
» It should be stable both physically and
chemically in Invivo & invitro conditions.
» Restrict drug distribution to non-target cells or
tissues or organs & should have uniform
distribution.
» Controllable & Predicate rate of drug release. 8

9. » Drug release should not effect drug action
» Specific Therapeutic amount of drug release must be
possessed
» Carriers used must be biodegradable or readily
eliminated from the body without any problem and no
carrier induced modulation in disease state.
» The preparation of the delivery system should be easy
or reasonable
» simple, reproducible & cost effective.
9

10. A : Cross Linking Methods
» 1) By Cross-linking of Amphiphilic Macromolecules
» 2) By Crosslinking in W/O Emulsion
» 3) By Emulsion chemical dehydration
» 4) By Phase Separation
» 5) By pH lnduced Aggregation
B : Polymerization Methods
» 1) Emulsion polymerization
» 2) Dispersion polymerization
10

11. » Nanoparticles can be prepared from Amphiphilic macromolecules,
proteins and polysaccharides (which have affinity for aqueous and
lipid solvents).
» The method involves Aggregation of Amphiphiles followed by
stabilization either by heat denaturation or chemical cross-linking
2) By Cross linking in W/O Emulsion
» Emulsification of bovine serum albumin (BSA) OR
human serum albumin (HSA) or protein aqueous
solution in oil using high-pressure homogenization or high
frequency sonication.
11

12. Aqueous
protein (BSA)
Oil
W/O emulsion
Dilution with preheated oil (100oC)
(Heat cross-linking)
Or Addition of crosslinking agent
(Chemical cross-linking)
Centrifugation and isolation of
nanoparticles
Emulsification using high-
pressure homogenization or high
frequency sonication
Surfactant
12

13. » Stabilization can also be achieved by emulsion chemical
dehydration.
» Hydroxy propyl cellulose solution in chloroform is used
as a continuous phase,
» while a chemical dehydrating agent,
» 2,2, di-methyl propane is used to disperse into the
internal aqueous phase to form an Emulsion.
» ADV: The method avoid coalescence of droplets and
could produce nanoparticles of smaller size (300nm), 13

14. » The protein or polysaccharide from an aqueous phase can be
Desolvated by :
˃ A) pH change
˃ B) Change in temperature
˃ C) Addition of appropriate counter ions e.g. alginate
14

15. Aqueous phase(protein aqueous solution)
Protein aggregates (Coacervates)
Protein colloidal dispersion
Nanoparticles dispersion
(External aqueous phase) 200nm
Desolvation
Resolvation
Cross-linking
Heat to 40o C , subsequent cooling to 4O C
for 24h.
15

16. » Gelatin Nanospheres were prepared by :
Gelatin & tween 20 were dissolved in aq. phase & pH
of the solution was adjusted to optimum value.
The clear solution so obtained was heated to 400C
followed by its quenching at 40C for 24hrs &
subsequently left at ambient temperature for 48hrs.
The sequential temperature treatment resulted into a
colloidal dispersion of aggregated gelatin. The aggregates
were finally cross linked using glutaraldehyde as cross
linking agent the optimum pH was 5.5- 6.5.values
below 5.5 produced no aggregation while above 6.5 an
uncontrolled aggregation led to the formation of larger
nanospheres
16

17. 1) Emulsion polymerization :
» IT CONSISTS OF :
» A] Micellar nucleation and polymerization :
Monomer is insoluble in continuous phase.(O/W phase)
Aqueous phase
» B] Homogenous nucleation and polymerization :
Monomer is soluble in continuous phase.(W/O phase)
Organic phase.
17

18. Monomer bearing Nucleated micelle Stabilized polymeric micelle
nanospheres
Catalyst
Monomer dropletCatalystDrug Monomer
monomer supply
(micelle) (nanospheres)
18

19. 19

20. lsolation of nanospheres
Oligomers aggregate &
precipitates
Further, By chemical initiation
(ammonium or potassium per oxo disulphate)
(Acrylamide or Methyl methacrylate) Monomer is dissolved
in an aqueous medium
Heated to above 65 C
20

21. Solvent Evaporation Method

22. Solvent Displacement Method

23. 23
Salting out of Polymer

24. PARAMETER METHOD
1) Particle size - Photon correlation
spectroscopy
- Laser defractometry
- Scanning electron
microscopy
2) Molecular weight - Gel Chromatography
3) Charge determination - Laser Doppler
Anemometry
- Zeta potentiometer 24

25. 4) Density - Helium compression
pynometry
5) Crystallinity - X-ray diffraction &
Differential scanning
Calorimetry,
Thermogravimetry
6) Hydrophobicity - Hydrophobic
interaction,
Chromatography
7) Surface element analysis - X-ray, photon
electron 25

26. 8) Specific Surface Area :
specific surface area A = 6/Density x diameter of particle
9) Invitro Release :
> Diffusion Cell .
> Recently Introduced Modified Ultra Filtration Technique.
> Media Used : Phosphate Buffer
10) Nanoparticle Yield :
% yield = Actual weight of Product X 100
Total weight of Drug and Excipients
26

27. 1) Widely used in case of Cancer Therapy.
2) In lntracellular Targeting
3) Used for Prolonged Systemic Circulation.
4) As a Vaccine Adjuvant.
5) In Case of Ocular delivery.
6) Used in DNA Delivery.
7) It is used in case of Oligonucleotide delivery.
8) Enzyme immunoassays
9) Radio-imaging.
10) To cross BBB. 27

28. 28
» Applications
Application Purpose Material
Cancer therapy Targeting, Reduced toxicity,
enhance uptake of anti-tumor
agent
Polyalkylcyanoacrylate with
anticancer agent
Intra cellular targeting Target reticuloendothelial
system for intracellular
infection
Poly alkyl cyanoarylate
Vaccine adjuvant Prolong systemic drug effect.
Enhance immune response
Poly methyl metha acrylate
nanoparticles with vaccines
DNA delivery Enhanced bioavailability and
significantly higher expression
level
DNA gelatin nanoparticles,
DNA chitosan
nanoparticles
Ocular delivery Improved retention of the drug
and reduced washed out.
Poly alkyl cyanoacrylate
nanoparticles , anti-
inflammatory agent

29. 29

30. » Targetted and controlled drug delivery by S.P. VYAS and
R.K. KHAR
» Jain N.K. “Advances in controlled and novel Drug Delivery”,
CBS publisher & Distributers, Edition 1st 2001, Pg. 408
» Nanotechnology in drug delivery - A Review, Indian Drugs,
Issue 11,november 2011.
» http://en.wikipedia.org/wiki/Nanoparticle
» http://www.pharmainfo.net/reviews/nanoparticles-review
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