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DENDRIMERS
NAMITHA CHANDRAN
M.Sc Biopolymer science
1
INTRODUCTION
 Dendrimers are repetitively branched molecules
 The name comes from Greek word “dendron”
which means “tree”.
 Also called as ‘’arborols/ cascade molecules’’.
 They are family of nanosized, highly branched
three dimensional molecules.
 Dendrimers are highly defined
nanoparticles.
2
STRUCTURE OF DENDRIMERS
 Dendrimers are built from a starting atom,
such as nitrogen, to which carbon and other
elements are added by a repeating series of
chemical reactions that produce a spherical
branching structure.
 As the process repeats, successive layers
are added, and the sphere can be
expanded to the size required by the
investigator.
 The result is a spherical macromolecular
structure whose size is similar to albumin
and hemoglobin
3
STRUCTURE OF DENDRIMER
 Basic dendrimer components are
1) An interior core
2) Interior layers composed of repeating units radically
attached to cores.
3) Exterior layer (terminal functionality) attached to interior
generations.
4
3D STRUCTURE OF DENDRIMER
5
IDEAL PROPERTIES OF
DENDRIMERS
1) Inert and non-toxic.
2) Biodegradable.
3) Non-immunogenic.
4) Able to cross barriers such as intestine, blood-tissue
barriers, cell membranes etc/
5) Able to stay in circulation for the time needed to have a
clinical effect.
6) Able to target to specific structures
7) Compatible with guest molecules.
8) Must protect the drug until it reaches to the desired site of
action and release the drug.
6
PHYSICOCHEMICAL PROPERTIES
OF DENDRIMERS
 Nanoscale size.
 high solubility, miscibility and reactivity due to the
presence of many chain ends.
 These carriers have significantly lower viscosity
than linear polymers.
 Size and molecular weight can be controlled during
synthesis.
7
CHARACTRIZATION OF
DENDRITIC POLYMERS
 Spectroscopy -UV-Visible, IR, NMR.
 Microscopy - TEM , SEM.
 physical properties – DSC,DMA,TGA
 Scattering techniques.
 Electrical techniques.
 Solubility .
 Determination of Melting Point .
 Elemental Analysis (Nitrogen).
8
SYNTHESIS OF DENDRIMERS
9
DENDRIMER
SYNTHESIS
Divergent method
Convergent method
DIVERGENT METHOD
 Divergent method was introduced by Tomali.
 dendrimer grows outwards from a multifunctional
core molecule.
 The core molecule reacts with monomer molecules
containing one reactive and two dormant groups
giving the first generation dendrimer.
 Then the new periphery of the molecule is activated
for reactions with more monomers.
 The process is repeated for several generations
and a dendrimer is built layer after layer.
10
DIVERGENT METHOD
11
DIVERGENT METHOD
 DISADVANTAGE
1. Can cause trailing generations.
2. Difficult to purify the product.
3. Because the relative size differences
between perfect and imperfect
dendrimers is very small.
12
CONVERGENT METHOD
 Dendrimer grows starting from end groups and
progresses inward.
 Method makes impurity removal easier
monodisperse dendrimers are obtained.
 But stearic effects along the core limits the size.
13
OVERVIEW
14
TYPES OF DENDRIMERS
15
PAMAM DENDRIMER
 PAMAM or Poly (Amido Amine) dendrimers are
spheroidal or ellipsoidal in shape.
 These are synthesized by the divergent method
using ammonia or ethylenediamine as a starting
material.
 The high solubility and reactivity of these are due to
presence of a number of functional end groups and
empty internal cavities.
 Commercially available as methanol solutions.
16
PAMAM DENDRIMER
 Starburst is a trademark name for a sub-class of
PAMAM dendrimers based on a trisaminoethylene-
imine core.
17
POLY (AMIDO AMINE
ORGANOSILICON)
 PAMAMOS are silicon containing first commercial
dendrimers.
 These are inverted unimolecular micelles
 it consist of hydrophilic, nucleophilic
polyamidoamine (PAMAM) interiors and
hydrophobic organosilicon (OS) exteriors.
 These dendrimers are exceptionally useful
precursors for the preparation of honeycomb-like
networks with nanoscopic PAMAMOS domains.
18
POLY (AMIDO AMINE ORGANOSILICON)
19
POLY (PROPYLENE IMINE)/ POLY
(PROPYLENE AMINE)
 PPI Dendrimer is one of the oldest known
dendrimer developed initially by Vogtle.
 structure
 Core- diamino butane
 Interior- tertiary propylene amines
 End groups- primary amines
 It referred as “DAB-dendrimers”. where DAB refers
to the core structure.
 It used in the field of material science and biology.
These are widely available as AstramolTM
20
TECTO DENDRIMER
 These are composed of a core dendrimer, which
surrounded by other dendrimers,
 each dendrimer perform a specific function.
 It used in smart therapeutic system.
 which can simultaneously diagnose the diseased
state and deliver API to the recognized diseased
cell
21
TECTO DENDRIMER
 Different compounds perform varied functions, such
as diseased cell recognition, diagnosis of disease
state, drug delivery, reporting outcomes of therapy,
etc..,
22
LIQUID CRYSTALLINE
DENDRIMERS
 These are highly-branched oligomer or polymer of
dendritic structure.
 It containing mesogenic groups that can display
mesophase behaviour.
 They consist of mesogenic (liquid crystalline)
monomers, e.g. mesogen functionalized
carbosilane dendrimers.
 These dendrimers consists of multiple copies of a
particular functional group on their surface.
23
CHIRAL DENDRIMERS
 Chiral dendrimers produced using different but
chemically similar branches.
 These braches attached to the chiral core.
 Their potential use as chiral hosts for enantiomeric
resolutions and as chiral catalysts for asymmetric
synthesis .
24
HYBRID DENDRIMERS
 These are hybrids (block or graft polymers) of
dendritic and linear polymers having characters of
both.
 these are obtained by complete
monofunctionalization of the peripheral amines of a
"zerogeneration" polyethyleneimine dendrimer.
 provide structurally diverse lamellar, columnar, and
cubic self organized lattices that are less readily
available from other modified dendritic structures
25
AMPHIPHILIC DENDRIMERS
 These are composed of two segregated sites of
chain end.
 In these dendrimers one half is electron donating
and the other half is electron withdrawing.
26
MICELLAR DENDRIMERS
 These are unimolecular micelles of water soluble
hyper branched polyphenylenes micelles.
27
PEPTIDE DENDRIMERS
 These dendrimers consists of amino acids as
branching or interior unit. It is a dendron like
molecular construct based upon a polylysine
skeleton.
 This type of dendrimer was introduced by J. P. Tam
in 1988.
 It use in biological applications, such as in vaccine
and diagnostic research.
28
FRECHET-TYPE DENDRIMERS
 It is a more recent type of dendrimer developed by
Hawker and Frechet based on polybenzyl ether
hyper branched skeleton.
 In these carboxylic acid groups is surface groups,
which serving as a good anchoring point for further
surface fictionalization.
 Polar surface groups increase the solubility of this
hydrophobic dendrimer type in polar solvents or
aqueous media.
29
APPLICATION OF DENDRIMERS
30
APPLICATION OF DENTRIMERS
31
NON MEDICALMEDICAL
MEDICAL APPLICATIONS
 Dendrimers in biomedicafield
 Dendrimers are analogous to protein,
enzymes and viruses .
 PAMAM dendrimers can be used to target
tumour cells.
 Targeting groups can be conjugated to the
host dendrimers surface.
32
MEDICAL APPLICATIONS
 Dendrimer as magnetic resonance
imaging contrast agents
 Dendrimer based metal chelates act as
a magnetic resonance imaging contrast
agent.
 Larger hydrophilic agents were useful for
blood and lymphatic imaging.
 Smaller sized used for kidney imging
33
MEDICAL APPLICATIONS
 Dendrimers in Antitumor Therapy
34
MEDICAL APPLICATIONS
 Dendrimers in gene transfection
o DNA is coupled to a nanoparticle
of inert solid, which is then directly
targeted to the cell nucleus.
o It is used for studying mutations
and regulation processes of genes
or inducing over expression of
desired proteins.
35
MEDICAL APPLICATIONS
 Dendrimers in gene transfection
36
MEDICAL APPLICATIONS
 Dendrimers as Biomimics
 It mimic wide variety of bio molecules and
also create micro environment.
 which makes artificial catalytic sites or
cavities possessing different properties
for construction of enzyme mimics.
37
MEDICAL APPLICATIONS
 In-vivo degradation of drug dendrimer
38
MEDICAL APPLICATIONS
 Drug delivery
39
Due to change in temperature
MEDICAL APPLICATIONS
40
oDue to change in pH
NON MEDICAL APPLICATIONS
 Dendrimers as catalysts/enzymes
 The combination of high surface area and high
solubility makes dendrimers useful as nanoscale
catalysts.
 Dendrimershave a multifunctional surface and all
catalytic sites are always exposed towards the
reaction mixture.
 Some popular dendrimeric catalysts are terminated
soluble polycarbosilane dendrimers in diamino
arylnickel (II) complexes
41
NON MEDICAL APPLICATIONS
Dendrimers for additives, printing inks and paints
 dendritic polymers ensure uniform adhesion of ink
to polar and non-polar foils.
 Dendritic polymers used in polyurethane paints
impart surface hardness, scratch resistance,
chemical resistance, light, fastness, weathering
resistance as well as high gloss.
42
NON MEDICAL APPLICATIONS
Dendrimers as a separating agent
 Dendrimer is able to form micelle structure.
 which can be easily separated and recovered by
ultra filtration membrane.
 These micelles provide high functional density at
the surface of the particle, high surface area and
ease of separation for isolation and regeneration of
the compound.
 Polyamidoamine (PAMAM) dendrimers are used as
chelating agent.
43
NON MEDICAL APPLICATIONS
Industrial Processes
 Dendrimers can encapsulate insoluble
materials, such as metals, and transport
them into a solvent within their interior.
 Cooper et. al., 1997 synthesized fluorinated
dendrimers, soluble in supercritical CO2
and can be used to extract strongly
hydrophilic compounds from water into
liquid CO2.
 Hazardous organic solvents are replaced by
liquid CO2. 44
FUTURE DEVELOPMENTS
To reducing the synthesis cost.
Exploiting the new applications of
dendritic polymers in the other fields of
membrane.
Improve the synthesis method.
Develop more medical application.
45
MARKETED PRODUCTS AVAILABLE
 SuperFect TM(Qiagen) is a famous gene
transfection agent applicable to a broad range of
cell lines.
 Starpharma has already taken a dendrimer-based
drug into clinical trials conducted to US FDA
requirements
 VivaGel(R) microbicide and has anti HIV property
is currently in Phase 3 clinical trial
 Poly (propylene imine) dendrimers are available
under name Astramol TM.
46
CONCLUSION
Among the nanoparticulate carriers, dendrimers
have tremendous potential in the applications
involving multifunctional nanoparticulate systems
combining targeting, imaging, diagnostics and
therapy. Thus, this multifunctional, unique
nanoparticulate carrier has the potential to detect
diseases, deliver medications, and monitor the
ability to change the current scenario of cancer
research and diagnosis in real time.
47
48

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Dendrimers and its applications

  • 2. INTRODUCTION  Dendrimers are repetitively branched molecules  The name comes from Greek word “dendron” which means “tree”.  Also called as ‘’arborols/ cascade molecules’’.  They are family of nanosized, highly branched three dimensional molecules.  Dendrimers are highly defined nanoparticles. 2
  • 3. STRUCTURE OF DENDRIMERS  Dendrimers are built from a starting atom, such as nitrogen, to which carbon and other elements are added by a repeating series of chemical reactions that produce a spherical branching structure.  As the process repeats, successive layers are added, and the sphere can be expanded to the size required by the investigator.  The result is a spherical macromolecular structure whose size is similar to albumin and hemoglobin 3
  • 4. STRUCTURE OF DENDRIMER  Basic dendrimer components are 1) An interior core 2) Interior layers composed of repeating units radically attached to cores. 3) Exterior layer (terminal functionality) attached to interior generations. 4
  • 5. 3D STRUCTURE OF DENDRIMER 5
  • 6. IDEAL PROPERTIES OF DENDRIMERS 1) Inert and non-toxic. 2) Biodegradable. 3) Non-immunogenic. 4) Able to cross barriers such as intestine, blood-tissue barriers, cell membranes etc/ 5) Able to stay in circulation for the time needed to have a clinical effect. 6) Able to target to specific structures 7) Compatible with guest molecules. 8) Must protect the drug until it reaches to the desired site of action and release the drug. 6
  • 7. PHYSICOCHEMICAL PROPERTIES OF DENDRIMERS  Nanoscale size.  high solubility, miscibility and reactivity due to the presence of many chain ends.  These carriers have significantly lower viscosity than linear polymers.  Size and molecular weight can be controlled during synthesis. 7
  • 8. CHARACTRIZATION OF DENDRITIC POLYMERS  Spectroscopy -UV-Visible, IR, NMR.  Microscopy - TEM , SEM.  physical properties – DSC,DMA,TGA  Scattering techniques.  Electrical techniques.  Solubility .  Determination of Melting Point .  Elemental Analysis (Nitrogen). 8
  • 10. DIVERGENT METHOD  Divergent method was introduced by Tomali.  dendrimer grows outwards from a multifunctional core molecule.  The core molecule reacts with monomer molecules containing one reactive and two dormant groups giving the first generation dendrimer.  Then the new periphery of the molecule is activated for reactions with more monomers.  The process is repeated for several generations and a dendrimer is built layer after layer. 10
  • 12. DIVERGENT METHOD  DISADVANTAGE 1. Can cause trailing generations. 2. Difficult to purify the product. 3. Because the relative size differences between perfect and imperfect dendrimers is very small. 12
  • 13. CONVERGENT METHOD  Dendrimer grows starting from end groups and progresses inward.  Method makes impurity removal easier monodisperse dendrimers are obtained.  But stearic effects along the core limits the size. 13
  • 16. PAMAM DENDRIMER  PAMAM or Poly (Amido Amine) dendrimers are spheroidal or ellipsoidal in shape.  These are synthesized by the divergent method using ammonia or ethylenediamine as a starting material.  The high solubility and reactivity of these are due to presence of a number of functional end groups and empty internal cavities.  Commercially available as methanol solutions. 16
  • 17. PAMAM DENDRIMER  Starburst is a trademark name for a sub-class of PAMAM dendrimers based on a trisaminoethylene- imine core. 17
  • 18. POLY (AMIDO AMINE ORGANOSILICON)  PAMAMOS are silicon containing first commercial dendrimers.  These are inverted unimolecular micelles  it consist of hydrophilic, nucleophilic polyamidoamine (PAMAM) interiors and hydrophobic organosilicon (OS) exteriors.  These dendrimers are exceptionally useful precursors for the preparation of honeycomb-like networks with nanoscopic PAMAMOS domains. 18
  • 19. POLY (AMIDO AMINE ORGANOSILICON) 19
  • 20. POLY (PROPYLENE IMINE)/ POLY (PROPYLENE AMINE)  PPI Dendrimer is one of the oldest known dendrimer developed initially by Vogtle.  structure  Core- diamino butane  Interior- tertiary propylene amines  End groups- primary amines  It referred as “DAB-dendrimers”. where DAB refers to the core structure.  It used in the field of material science and biology. These are widely available as AstramolTM 20
  • 21. TECTO DENDRIMER  These are composed of a core dendrimer, which surrounded by other dendrimers,  each dendrimer perform a specific function.  It used in smart therapeutic system.  which can simultaneously diagnose the diseased state and deliver API to the recognized diseased cell 21
  • 22. TECTO DENDRIMER  Different compounds perform varied functions, such as diseased cell recognition, diagnosis of disease state, drug delivery, reporting outcomes of therapy, etc.., 22
  • 23. LIQUID CRYSTALLINE DENDRIMERS  These are highly-branched oligomer or polymer of dendritic structure.  It containing mesogenic groups that can display mesophase behaviour.  They consist of mesogenic (liquid crystalline) monomers, e.g. mesogen functionalized carbosilane dendrimers.  These dendrimers consists of multiple copies of a particular functional group on their surface. 23
  • 24. CHIRAL DENDRIMERS  Chiral dendrimers produced using different but chemically similar branches.  These braches attached to the chiral core.  Their potential use as chiral hosts for enantiomeric resolutions and as chiral catalysts for asymmetric synthesis . 24
  • 25. HYBRID DENDRIMERS  These are hybrids (block or graft polymers) of dendritic and linear polymers having characters of both.  these are obtained by complete monofunctionalization of the peripheral amines of a "zerogeneration" polyethyleneimine dendrimer.  provide structurally diverse lamellar, columnar, and cubic self organized lattices that are less readily available from other modified dendritic structures 25
  • 26. AMPHIPHILIC DENDRIMERS  These are composed of two segregated sites of chain end.  In these dendrimers one half is electron donating and the other half is electron withdrawing. 26
  • 27. MICELLAR DENDRIMERS  These are unimolecular micelles of water soluble hyper branched polyphenylenes micelles. 27
  • 28. PEPTIDE DENDRIMERS  These dendrimers consists of amino acids as branching or interior unit. It is a dendron like molecular construct based upon a polylysine skeleton.  This type of dendrimer was introduced by J. P. Tam in 1988.  It use in biological applications, such as in vaccine and diagnostic research. 28
  • 29. FRECHET-TYPE DENDRIMERS  It is a more recent type of dendrimer developed by Hawker and Frechet based on polybenzyl ether hyper branched skeleton.  In these carboxylic acid groups is surface groups, which serving as a good anchoring point for further surface fictionalization.  Polar surface groups increase the solubility of this hydrophobic dendrimer type in polar solvents or aqueous media. 29
  • 32. MEDICAL APPLICATIONS  Dendrimers in biomedicafield  Dendrimers are analogous to protein, enzymes and viruses .  PAMAM dendrimers can be used to target tumour cells.  Targeting groups can be conjugated to the host dendrimers surface. 32
  • 33. MEDICAL APPLICATIONS  Dendrimer as magnetic resonance imaging contrast agents  Dendrimer based metal chelates act as a magnetic resonance imaging contrast agent.  Larger hydrophilic agents were useful for blood and lymphatic imaging.  Smaller sized used for kidney imging 33
  • 34. MEDICAL APPLICATIONS  Dendrimers in Antitumor Therapy 34
  • 35. MEDICAL APPLICATIONS  Dendrimers in gene transfection o DNA is coupled to a nanoparticle of inert solid, which is then directly targeted to the cell nucleus. o It is used for studying mutations and regulation processes of genes or inducing over expression of desired proteins. 35
  • 36. MEDICAL APPLICATIONS  Dendrimers in gene transfection 36
  • 37. MEDICAL APPLICATIONS  Dendrimers as Biomimics  It mimic wide variety of bio molecules and also create micro environment.  which makes artificial catalytic sites or cavities possessing different properties for construction of enzyme mimics. 37
  • 38. MEDICAL APPLICATIONS  In-vivo degradation of drug dendrimer 38
  • 39. MEDICAL APPLICATIONS  Drug delivery 39 Due to change in temperature
  • 41. NON MEDICAL APPLICATIONS  Dendrimers as catalysts/enzymes  The combination of high surface area and high solubility makes dendrimers useful as nanoscale catalysts.  Dendrimershave a multifunctional surface and all catalytic sites are always exposed towards the reaction mixture.  Some popular dendrimeric catalysts are terminated soluble polycarbosilane dendrimers in diamino arylnickel (II) complexes 41
  • 42. NON MEDICAL APPLICATIONS Dendrimers for additives, printing inks and paints  dendritic polymers ensure uniform adhesion of ink to polar and non-polar foils.  Dendritic polymers used in polyurethane paints impart surface hardness, scratch resistance, chemical resistance, light, fastness, weathering resistance as well as high gloss. 42
  • 43. NON MEDICAL APPLICATIONS Dendrimers as a separating agent  Dendrimer is able to form micelle structure.  which can be easily separated and recovered by ultra filtration membrane.  These micelles provide high functional density at the surface of the particle, high surface area and ease of separation for isolation and regeneration of the compound.  Polyamidoamine (PAMAM) dendrimers are used as chelating agent. 43
  • 44. NON MEDICAL APPLICATIONS Industrial Processes  Dendrimers can encapsulate insoluble materials, such as metals, and transport them into a solvent within their interior.  Cooper et. al., 1997 synthesized fluorinated dendrimers, soluble in supercritical CO2 and can be used to extract strongly hydrophilic compounds from water into liquid CO2.  Hazardous organic solvents are replaced by liquid CO2. 44
  • 45. FUTURE DEVELOPMENTS To reducing the synthesis cost. Exploiting the new applications of dendritic polymers in the other fields of membrane. Improve the synthesis method. Develop more medical application. 45
  • 46. MARKETED PRODUCTS AVAILABLE  SuperFect TM(Qiagen) is a famous gene transfection agent applicable to a broad range of cell lines.  Starpharma has already taken a dendrimer-based drug into clinical trials conducted to US FDA requirements  VivaGel(R) microbicide and has anti HIV property is currently in Phase 3 clinical trial  Poly (propylene imine) dendrimers are available under name Astramol TM. 46
  • 47. CONCLUSION Among the nanoparticulate carriers, dendrimers have tremendous potential in the applications involving multifunctional nanoparticulate systems combining targeting, imaging, diagnostics and therapy. Thus, this multifunctional, unique nanoparticulate carrier has the potential to detect diseases, deliver medications, and monitor the ability to change the current scenario of cancer research and diagnosis in real time. 47
  • 48. 48