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» 1. INTRODUCTION
» 2. CONCEPT
» 3. ADV AND DISADV
» 4. IDEAL CHARACTERISTICS
» 5. METHOD OF PREPARATION
» 6. CHARACTERIZATION
» 7. EVALUATION
» 8. APPLICATIONS
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.
» 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;
» 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 components,
such as polymers (synthetic or natural)
» 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
» 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.
» It should be biochemical inert , non toxic and
non-immunogenic.
» It should be stable both physically and
chemically in in-vivo & in-vitro conditions.
» Restrict drug distribution to non-target cells or
tissues or organs & should have uniform
distribution.
» Controllable & Predicate rate of drug release.
» 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.
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 induced Aggregation
B : Polymerization Methods
» 1) Emulsion polymerization
» 2) Dispersion polymerization
C : Polymer precipitation methods
» 1) Solvent evaporation
» 2) Solvent displacement
» 3) Salting out
» 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.
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
» 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),
» 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
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
» 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
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.
Monomer bearing Nucleated micelle Stabilized polymeric micelle
nanospheres
Catalyst
Monomer dropletCatalystDrug Monomer
monomer supply
(micelle) (nanospheres)
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
Organic phase
Solvent, drug, polymer
Aqueous phase,
water, stabilizer
nanoparticles
Sonication, homogenisation
W/O emulsion, aqueous phase
with stabilizer (PVA)
W/O/W emulsion,
solvent extraction/evaporation
Ultracentrifugation / probe sonication
1) Solvent Evaporation Method
Aqueous phase
Water, polaxamer 188
Aqueous phase
Water, polaxamer 188
Organic phase
Organic solvent
Polymer, drug
Organic phase
Organic solvent
Polymer, drug
nanospheres nanocapsules
Magnetic stirring
2) Solvent Displacement method
3) Salting out Method
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
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
8) Invitro Release :
> Diffusion Cell .
> Recently Introduced Modified Ultra Filtration Technique.
> Media Used : Phosphate Buffer
9) Nanoparticle Yield :
% yield = Actual weight of Product X 100
Total weight of Drug and Excipients
» 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.
» TARGETED AND CONTROLLED DRUG DELIVERY
by S.P. VYAS and R.K. KHAR
» Internet- google.net
Nanoparticle by ankit parulkar

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Nanoparticle by ankit parulkar

  • 1.
  • 2. » 1. INTRODUCTION » 2. CONCEPT » 3. ADV AND DISADV » 4. IDEAL CHARACTERISTICS » 5. METHOD OF PREPARATION » 6. CHARACTERIZATION » 7. EVALUATION » 8. APPLICATIONS
  • 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.
  • 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;
  • 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 components, such as polymers (synthetic or natural)
  • 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
  • 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.
  • 8. » It should be biochemical inert , non toxic and non-immunogenic. » It should be stable both physically and chemically in in-vivo & in-vitro conditions. » Restrict drug distribution to non-target cells or tissues or organs & should have uniform distribution. » Controllable & Predicate rate of drug release.
  • 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.
  • 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 induced Aggregation B : Polymerization Methods » 1) Emulsion polymerization » 2) Dispersion polymerization C : Polymer precipitation methods » 1) Solvent evaporation » 2) Solvent displacement » 3) Salting out
  • 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.
  • 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
  • 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),
  • 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
  • 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
  • 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.
  • 18. Monomer bearing Nucleated micelle Stabilized polymeric micelle nanospheres Catalyst Monomer dropletCatalystDrug Monomer monomer supply (micelle) (nanospheres)
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  • 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. Organic phase Solvent, drug, polymer Aqueous phase, water, stabilizer nanoparticles Sonication, homogenisation W/O emulsion, aqueous phase with stabilizer (PVA) W/O/W emulsion, solvent extraction/evaporation Ultracentrifugation / probe sonication 1) Solvent Evaporation Method
  • 22. Aqueous phase Water, polaxamer 188 Aqueous phase Water, polaxamer 188 Organic phase Organic solvent Polymer, drug Organic phase Organic solvent Polymer, drug nanospheres nanocapsules Magnetic stirring 2) Solvent Displacement method
  • 23. 3) Salting out Method
  • 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
  • 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
  • 26. 8) Invitro Release : > Diffusion Cell . > Recently Introduced Modified Ultra Filtration Technique. > Media Used : Phosphate Buffer 9) Nanoparticle Yield : % yield = Actual weight of Product X 100 Total weight of Drug and Excipients
  • 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.
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  • 30. » TARGETED AND CONTROLLED DRUG DELIVERY by S.P. VYAS and R.K. KHAR » Internet- google.net