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20/03/2008 Dept. of Pharmaceutics 1
Nanotechnology Based Drug Delivery
Dr. Basavaraj K. Nanjwade M.Pharm., Ph.D
Associate Professor
Department of Pharmaceutics
JN Medical College
KLE University
Belgaum-590010
20/03/2008 Dept. of Pharmaceutics 2
Applications of Nanotechnology
20/03/2008 Dept. of Pharmaceutics 3
Targeted Drug Delivery
20/03/2008 Dept. of Pharmaceutics 4
Nanoparticles for Drug Delivery
Metal-based nanoparticles
Lipid-based nanoparticles
Polymer-based nanoparticles
Biological nanoparticles
20/03/2008 Dept. of Pharmaceutics 5
Nanobiopharmaceuticals
In biopharmaceuticals, in addition to the
main technologies covered-liposomal,
monoclonal antibody-based, and polymer-
based technologies host of newer
technologies such as nanoparticles
including various nanodimensional entities
such as molecular imprinted polymers,
metallofullerenes, prodrug delivery, oral,
injectable and implantable, pulmonary, and
transdermal and transmucosal delivery
have come up.
20/03/2008 Dept. of Pharmaceutics 6
Drug Delivery Technology Important to
Pharma Industry
Drug delivery formulations involve low cost
research compared that for discovery of
new molecule,
Minimizing the drug use would significantly
reduce the effective cost of drug which
would give financial relief to the patients,
20/03/2008 Dept. of Pharmaceutics 7
Delivery systems increase commercial
opportunity by distinguishing a drug from
competitive threats posed by “me too”
drugs and
Novel means of delivery particularly using
nano-carriers, can allow branded drugs to
be rescued from abyss of generic
competition (may be called “resurrection of
drug”).
Drug Delivery Technology Important to
Pharma Industry
20/03/2008 Dept. of Pharmaceutics 8
SOME SIGNIFICANT ACHIEVEMENTS OF
NANODEVICES
Development of one dose a day ciprofloxacin using
nanotechnology
Tumor targeted taxol delivery using nanoparticles in
Phase 2 clinical trial stage
Improved ophthalmic delivery formulation using
smart hydrogel nanoparticles
Oral insulin formulation using nanoparticles carriers.
Liposomal based Amphotericin B formulation
20/03/2008 Dept. of Pharmaceutics 9
CHALLENGES
Prevention of drug from biological degradation
Effective Targeting
Patient Compliance
Cost effectiveness
Product life extension
20/03/2008 Dept. of Pharmaceutics 10
PRIORITY AREAS
Cancer Nanotechnology
(i) Diagnosis using Quantum
Dots
(ii) Tumor Targeted Delivery
(iii) Imaging
(iv) Cancer Gene Therapy
20/03/2008 Dept. of Pharmaceutics 11
PRIORITY AREAS
DNA Vaccines for parasitic, bacterial and
viral diseases
Oral and pulmonary routes for systemic
delivery of proteins and peptides
Nanotechnology in Tissue Engineering
20/03/2008 Dept. of Pharmaceutics 12
Drug Delivery Carriers
20/03/2008 Dept. of Pharmaceutics 13
Targeting Ligands
20/03/2008 Dept. of Pharmaceutics 14
Liposome's
20/03/2008 Dept. of Pharmaceutics 15
Liposome's
Their exterior lipid bilayer is very chemically reactive, thereby providing a
means to conveniently couple “tags” on a covalent basis.
Such “tags” can be antibodies, antigens, cell receptors, nucleic acid
probes, etc.
This provides significant versatility in assay formats (i.e., immunoassay,
receptor-based, nucleic acid probe, etc.) possible.
With diameters ranging in size from approximately 50 nm to 800 nm,
their aqueous core encapsulates up to millions of molecules of signal
generating “markers” that can be detected in a variety of different way.
A variety of different encapsulants are possible including visually
detectable dyes (since the lipid bilayer is transparent), optically and
fluorometrically detectable dyes, enzymes, and electroactive compounds.
This provides significant versatility in the detection schemes possible.
20/03/2008 Dept. of Pharmaceutics 16
Niosomes
20/03/2008 Dept. of Pharmaceutics 17
Niosomes
Niosomes, non-ionic surfactant vesicles, are widely studied as an
alternative to liposomes
These vesicles appear to be similar to liposomes in terms of their
physical properties
They are also prepared in the same way and under a variety of
conditions, from unilamellar or multilamellar structures.
Niosomes alleviate the disadvantages associated with liposomes,
such as chemical instability, variable purity of phospholipids and
high cost.
They have the potential for controlled and targated drug delivery
Niosomes enhanced the penetration of drugs
20/03/2008 Dept. of Pharmaceutics 18
Nanopowder
20/03/2008 Dept. of Pharmaceutics 19
Nanopowder
Nanopowders are powders composed of
nanoparticles, that is particles having an average
diameter below 50 nanometers (nm).
A jar of a true nanopowder when emptied from
chest height to toward the floor will disperse into
the air before reaching the floor.
Most manufacturers of “nanopowders” produce
micropowder assemblies of nanoparticles but the
powder itself is rarely a nanopowder.
Such compounds have two or more different
cations (positively charged elements) in their
chemical formula. An example of a complex
compound is calcium titanate (CaTiO3).
20/03/2008 Dept. of Pharmaceutics 20
Nanocluster
20/03/2008 Dept. of Pharmaceutics 21
Nanocluster
One of the central themes in nanoscience
research is to synthesize high quality
nanoparticles with precise control over
particle size, shape, structure, and
composition.
For inorganic nanoparticles (e.g. metal
and semiconductor), two regimes are of
particular interest, that is, nanoclusters in
a size range from subnanometer to ~2 nm
and nanocrystals (typically 2-100 nm).
20/03/2008 Dept. of Pharmaceutics 22
Nanocrystals
20/03/2008 Dept. of Pharmaceutics 23
Nanocrystals
When the size of the material is reduced to less than 100
nanometers, the realm of quantum physics takes over and
materials begin to demonstrate entirely new properties.
Nano-design of drugs by various techniques like milling,
high pressure homogenization, controlled precipitation etc.,
are explored to produce, drug nanocrystals, nanoparticles,
nanoprecipitates, nanosuspensions (which for ease of
understanding commonly mentioned as nanocrystals).
As decreased size will increase the solubility of drugs
hence, this technology is explored to increase oral
bioavailability of sparingly water soluble drugs.
20/03/2008 Dept. of Pharmaceutics 24
Micelle
20/03/2008 Dept. of Pharmaceutics 25
Micelle
Micelle is an aggregate of amphipathic molecules in water, with the
nonpolar portions in the interior and the polar portions at the exterior
surface, exposed to water.
Amphiphilic molecules form micelle above a particular concentration which
is called as critical micellar concentration (CMC).
Micelles are known to have an anisotropic water distribution within their
structure, means water concentration decreases from the surface towards
the core of the micelle, with a completely hydrophobic (water-excluded)
core.
Hydrophobic drugs can be encapsulated/solubalized, into inner core.
The spatial position of a solubilized drug in a micelle will depend on its
polarity, nonpolar molecules will be solubilized in the micellar core, and
substances with intermediate polarity will be distributed along the
surfactant molecules in certain intermediate
positions.
20/03/2008 Dept. of Pharmaceutics 26
Dendrimers
20/03/2008 Dept. of Pharmaceutics 27
Dendrimers
These branched macromolecules are constructed around a
simple core unit.
Dendrimers have a high degree of molecular uniformity,
narrow molecular weight distribution, specific size and
shape characteristics, and a highly- functionalized
terminal surface.
The manufacturing process is a series of repetitive steps
starting with a central initiator core. Each subsequent
growth step represents a new "generation" of polymer with
a larger molecular diameter, twice the number of reactive
surface sites, and approximately double the molecular
weight of the preceding generation.
20/03/2008 Dept. of Pharmaceutics 28
Polymeric Nanoparticles
20/03/2008 Dept. of Pharmaceutics 29
Polymeric Nanoparticles
In recent years, biodegradable polymeric
nanoparticles have attracted considerable
attention as potential drug delivery
devices in view of their applications in
drug targeting to particular
organs/tissues, as carriers of DNA
in gene therapy, and in their ability to
deliver proteins, peptides and genes
through a per oral route of administration.
20/03/2008 Dept. of Pharmaceutics 30
Carbon 60
20/03/2008 Dept. of Pharmaceutics 31
Carbon 60
C60 are spherical molecules about 1nm in
diameter, comprising 60 carbon atoms
arranged as 20 hexagons and 12 pentagons: the
configuration of a football.
Hence they find application as
NanoPharmaceuticals with large drug payload in
their cage like structure.
On the other hand with development of various
chemical substitutes for C60, it is possible to
develop functionalized C60 with better drug
targeting properties
20/03/2008 Dept. of Pharmaceutics 32
Carbon Nanotube
20/03/2008 Dept. of Pharmaceutics 33
Carbon Nanotube
Carbon nanotubes are adept at entering the
nuclei of cells and may one day be used to
deliver drugs and vaccines.
The modified nanotubes have so far only been
used to ferry a small peptide into the nuclei of
fibroblast cells.
But the researchers are hopeful that the
technique may one day form the basis for new
anti-cancer treatments, gene therapies and
vaccines.
20/03/2008 Dept. of Pharmaceutics 34
Equipments for Nanoparticles
1.Homogenizer
2.Ultra Sonicator
3.Mills
4.Spray Milling
5.Supercritical Fluid Technology
6.Electrospray
7.Ultracentrifugation
8.Nanofiltration
20/03/2008 Dept. of Pharmaceutics 35
Homogenizer & Ultra Sonicator
20/03/2008 Dept. of Pharmaceutics 36
Methods of Drug Delivery
20/03/2008 Dept. of Pharmaceutics 37
E-mail: bknanjwade@yahoo.co.in

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NanotechnologyBasedDrugDelivery.ppt

  • 1. 20/03/2008 Dept. of Pharmaceutics 1 Nanotechnology Based Drug Delivery Dr. Basavaraj K. Nanjwade M.Pharm., Ph.D Associate Professor Department of Pharmaceutics JN Medical College KLE University Belgaum-590010
  • 2. 20/03/2008 Dept. of Pharmaceutics 2 Applications of Nanotechnology
  • 3. 20/03/2008 Dept. of Pharmaceutics 3 Targeted Drug Delivery
  • 4. 20/03/2008 Dept. of Pharmaceutics 4 Nanoparticles for Drug Delivery Metal-based nanoparticles Lipid-based nanoparticles Polymer-based nanoparticles Biological nanoparticles
  • 5. 20/03/2008 Dept. of Pharmaceutics 5 Nanobiopharmaceuticals In biopharmaceuticals, in addition to the main technologies covered-liposomal, monoclonal antibody-based, and polymer- based technologies host of newer technologies such as nanoparticles including various nanodimensional entities such as molecular imprinted polymers, metallofullerenes, prodrug delivery, oral, injectable and implantable, pulmonary, and transdermal and transmucosal delivery have come up.
  • 6. 20/03/2008 Dept. of Pharmaceutics 6 Drug Delivery Technology Important to Pharma Industry Drug delivery formulations involve low cost research compared that for discovery of new molecule, Minimizing the drug use would significantly reduce the effective cost of drug which would give financial relief to the patients,
  • 7. 20/03/2008 Dept. of Pharmaceutics 7 Delivery systems increase commercial opportunity by distinguishing a drug from competitive threats posed by “me too” drugs and Novel means of delivery particularly using nano-carriers, can allow branded drugs to be rescued from abyss of generic competition (may be called “resurrection of drug”). Drug Delivery Technology Important to Pharma Industry
  • 8. 20/03/2008 Dept. of Pharmaceutics 8 SOME SIGNIFICANT ACHIEVEMENTS OF NANODEVICES Development of one dose a day ciprofloxacin using nanotechnology Tumor targeted taxol delivery using nanoparticles in Phase 2 clinical trial stage Improved ophthalmic delivery formulation using smart hydrogel nanoparticles Oral insulin formulation using nanoparticles carriers. Liposomal based Amphotericin B formulation
  • 9. 20/03/2008 Dept. of Pharmaceutics 9 CHALLENGES Prevention of drug from biological degradation Effective Targeting Patient Compliance Cost effectiveness Product life extension
  • 10. 20/03/2008 Dept. of Pharmaceutics 10 PRIORITY AREAS Cancer Nanotechnology (i) Diagnosis using Quantum Dots (ii) Tumor Targeted Delivery (iii) Imaging (iv) Cancer Gene Therapy
  • 11. 20/03/2008 Dept. of Pharmaceutics 11 PRIORITY AREAS DNA Vaccines for parasitic, bacterial and viral diseases Oral and pulmonary routes for systemic delivery of proteins and peptides Nanotechnology in Tissue Engineering
  • 12. 20/03/2008 Dept. of Pharmaceutics 12 Drug Delivery Carriers
  • 13. 20/03/2008 Dept. of Pharmaceutics 13 Targeting Ligands
  • 14. 20/03/2008 Dept. of Pharmaceutics 14 Liposome's
  • 15. 20/03/2008 Dept. of Pharmaceutics 15 Liposome's Their exterior lipid bilayer is very chemically reactive, thereby providing a means to conveniently couple “tags” on a covalent basis. Such “tags” can be antibodies, antigens, cell receptors, nucleic acid probes, etc. This provides significant versatility in assay formats (i.e., immunoassay, receptor-based, nucleic acid probe, etc.) possible. With diameters ranging in size from approximately 50 nm to 800 nm, their aqueous core encapsulates up to millions of molecules of signal generating “markers” that can be detected in a variety of different way. A variety of different encapsulants are possible including visually detectable dyes (since the lipid bilayer is transparent), optically and fluorometrically detectable dyes, enzymes, and electroactive compounds. This provides significant versatility in the detection schemes possible.
  • 16. 20/03/2008 Dept. of Pharmaceutics 16 Niosomes
  • 17. 20/03/2008 Dept. of Pharmaceutics 17 Niosomes Niosomes, non-ionic surfactant vesicles, are widely studied as an alternative to liposomes These vesicles appear to be similar to liposomes in terms of their physical properties They are also prepared in the same way and under a variety of conditions, from unilamellar or multilamellar structures. Niosomes alleviate the disadvantages associated with liposomes, such as chemical instability, variable purity of phospholipids and high cost. They have the potential for controlled and targated drug delivery Niosomes enhanced the penetration of drugs
  • 18. 20/03/2008 Dept. of Pharmaceutics 18 Nanopowder
  • 19. 20/03/2008 Dept. of Pharmaceutics 19 Nanopowder Nanopowders are powders composed of nanoparticles, that is particles having an average diameter below 50 nanometers (nm). A jar of a true nanopowder when emptied from chest height to toward the floor will disperse into the air before reaching the floor. Most manufacturers of “nanopowders” produce micropowder assemblies of nanoparticles but the powder itself is rarely a nanopowder. Such compounds have two or more different cations (positively charged elements) in their chemical formula. An example of a complex compound is calcium titanate (CaTiO3).
  • 20. 20/03/2008 Dept. of Pharmaceutics 20 Nanocluster
  • 21. 20/03/2008 Dept. of Pharmaceutics 21 Nanocluster One of the central themes in nanoscience research is to synthesize high quality nanoparticles with precise control over particle size, shape, structure, and composition. For inorganic nanoparticles (e.g. metal and semiconductor), two regimes are of particular interest, that is, nanoclusters in a size range from subnanometer to ~2 nm and nanocrystals (typically 2-100 nm).
  • 22. 20/03/2008 Dept. of Pharmaceutics 22 Nanocrystals
  • 23. 20/03/2008 Dept. of Pharmaceutics 23 Nanocrystals When the size of the material is reduced to less than 100 nanometers, the realm of quantum physics takes over and materials begin to demonstrate entirely new properties. Nano-design of drugs by various techniques like milling, high pressure homogenization, controlled precipitation etc., are explored to produce, drug nanocrystals, nanoparticles, nanoprecipitates, nanosuspensions (which for ease of understanding commonly mentioned as nanocrystals). As decreased size will increase the solubility of drugs hence, this technology is explored to increase oral bioavailability of sparingly water soluble drugs.
  • 24. 20/03/2008 Dept. of Pharmaceutics 24 Micelle
  • 25. 20/03/2008 Dept. of Pharmaceutics 25 Micelle Micelle is an aggregate of amphipathic molecules in water, with the nonpolar portions in the interior and the polar portions at the exterior surface, exposed to water. Amphiphilic molecules form micelle above a particular concentration which is called as critical micellar concentration (CMC). Micelles are known to have an anisotropic water distribution within their structure, means water concentration decreases from the surface towards the core of the micelle, with a completely hydrophobic (water-excluded) core. Hydrophobic drugs can be encapsulated/solubalized, into inner core. The spatial position of a solubilized drug in a micelle will depend on its polarity, nonpolar molecules will be solubilized in the micellar core, and substances with intermediate polarity will be distributed along the surfactant molecules in certain intermediate positions.
  • 26. 20/03/2008 Dept. of Pharmaceutics 26 Dendrimers
  • 27. 20/03/2008 Dept. of Pharmaceutics 27 Dendrimers These branched macromolecules are constructed around a simple core unit. Dendrimers have a high degree of molecular uniformity, narrow molecular weight distribution, specific size and shape characteristics, and a highly- functionalized terminal surface. The manufacturing process is a series of repetitive steps starting with a central initiator core. Each subsequent growth step represents a new "generation" of polymer with a larger molecular diameter, twice the number of reactive surface sites, and approximately double the molecular weight of the preceding generation.
  • 28. 20/03/2008 Dept. of Pharmaceutics 28 Polymeric Nanoparticles
  • 29. 20/03/2008 Dept. of Pharmaceutics 29 Polymeric Nanoparticles In recent years, biodegradable polymeric nanoparticles have attracted considerable attention as potential drug delivery devices in view of their applications in drug targeting to particular organs/tissues, as carriers of DNA in gene therapy, and in their ability to deliver proteins, peptides and genes through a per oral route of administration.
  • 30. 20/03/2008 Dept. of Pharmaceutics 30 Carbon 60
  • 31. 20/03/2008 Dept. of Pharmaceutics 31 Carbon 60 C60 are spherical molecules about 1nm in diameter, comprising 60 carbon atoms arranged as 20 hexagons and 12 pentagons: the configuration of a football. Hence they find application as NanoPharmaceuticals with large drug payload in their cage like structure. On the other hand with development of various chemical substitutes for C60, it is possible to develop functionalized C60 with better drug targeting properties
  • 32. 20/03/2008 Dept. of Pharmaceutics 32 Carbon Nanotube
  • 33. 20/03/2008 Dept. of Pharmaceutics 33 Carbon Nanotube Carbon nanotubes are adept at entering the nuclei of cells and may one day be used to deliver drugs and vaccines. The modified nanotubes have so far only been used to ferry a small peptide into the nuclei of fibroblast cells. But the researchers are hopeful that the technique may one day form the basis for new anti-cancer treatments, gene therapies and vaccines.
  • 34. 20/03/2008 Dept. of Pharmaceutics 34 Equipments for Nanoparticles 1.Homogenizer 2.Ultra Sonicator 3.Mills 4.Spray Milling 5.Supercritical Fluid Technology 6.Electrospray 7.Ultracentrifugation 8.Nanofiltration
  • 35. 20/03/2008 Dept. of Pharmaceutics 35 Homogenizer & Ultra Sonicator
  • 36. 20/03/2008 Dept. of Pharmaceutics 36 Methods of Drug Delivery
  • 37. 20/03/2008 Dept. of Pharmaceutics 37 E-mail: bknanjwade@yahoo.co.in