Definition, properties, applications

1. DENDRIMERS
PRESENTED BY:
SAMIKSHA SAWANT
M.PHARM(IP), 1st SEM
GUIDED BY : SHRUTI
SHRIKHANDE
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2. WHY DENDRIMERS?
They act as a carrier for :
Targeted drug delivery.
Controlled release of
drug
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3. WHAT ARE DENDRIMERS?
 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.
 Synthesis of polyamidoamine(PAMAM)
dendrimer in 1985 was a turning point.
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4. STRUCTURE OF DENDRIMER
1) An interior core
2) Interior layers composed of repeating units radically
attached to cores.
3) Exterior layer (terminal functionality) attached to
interior generations.
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5. 3D STRUCTURE OF DENDRIMER
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6. PROPERTIES OF DENDRIMERS
1) Monodispersity
2) Nanoscale size and shape
3) Viscosity
4) High aqueous solubility
5) High solubility in non polar solutions
6) Non crystalline and have low glass temperature
7) Low compressibility
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7. CHARACTRIZATION OF DENDRITIC
POLYMERS
1) Spectroscopy and spectroscopy methods.
2) Scattering techniques.
3) Electrical techniques.
4) Chromatographic techniques.
5) Microscopy.
6) Rheology, physical properties.
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8. SYNTHESIS OF DENDRIMERS
There are two methods of synthesizing dendrimers:
1) Divergent method
2) Convergent method
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9. DIVERGENT METHOD
 Dendrimer grows from core to periphery.
 The core molecule reacts with the monomer molecule
having two dormant and one reactive group.
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10. DIVERGENT METHOD
 Can cause trailing generations.
 Difficult to purify the product.
 Because the relative size differences between perfect
and imperfect dendrimers is very small.
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11. 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.
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12. CONVERGENT METHOD
 Small molecules come together and reaction proceeds
inward.
 Eventually the molecules become attached to the core.
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13. OVERVIEW
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14. TYPES OF DENDRIMERS
1) PAMAM dendrimers-They are synthesized by divergent
method starting with ammonia or ethylene diamine
initiator core reagent.
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15. USES OF PAMAM DENDRIMERS
 Simple PAMAM-drug complexes would affect a broad
spectrum of cells upon introduction to a living system
 PAMAM derivatized with folic acid is preferentially
taken up by cancer cell, which are known to over
express the folate receptor on their surfaces.
 Attaching additional treatment methods along with
the folic acid, such as boron
isotopes, cisplatin and methotrexate have proven
quite effective.
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16. • In gene therapy
Surface amine residues on PAMAM dendrimers bind to the phosphate
backbone of nucleic acids through charged interactions. Typically, G6-7
PAMAM dendrimers are used for gene tranfection; these dendrimers are
typically 6-10nm in length.
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17.  Pamamos dendrimer-radially
layered poly(amidoamine-
organosilicon)dendrimers
consist of
hydrophilic,nucleophilic
polyamidoamine interiors and
hydrophobic organosilicon
exterior.
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18. SYNTHESIS OF PAMAMOS
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19. DIFFERENT GENERATIONS OF SILICON
DENDRIMER
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20. PPI DENDRIMERS
 PPI dendrimers-poly-
Propylene Imine having
primary amines as end
groups, the dendrimer
interior consist of tertiary
tris-propylene amines.
 PPI dendrimers are
commercially available upto
G5 generation.
 Also called as POPAM or DAB
dendrimers.
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21. TECTO DENDRIMERS
 Composed of core dendrimer,
surrounded by dendrimers of
several steps to work as a
smart nanodevice.
 Perfoms disease cell
recognition, diagnosis of
disease, drug delivery etc.
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22. FRECHET TYPE DENDRIMER
 It is based on poly-benzyl ether hyper branched
skeleton. They have carboxylic acid groups as surface
groups.
 These groups serve as good anchoring points for
further surface functionalisation.
 Also act as polar groups to increase the solubility of
this hydrophobic dendrimer.
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23. AMPHIPHILIC DENDRIMERS
 They have hydrophobic interior core and hydrophilic
exterior.
 Hence are good carriers for drugs with poor solubility.
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24. MECHANISMS OF DRUG LOADING
1) Simple encapsulation
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25. MECHANISMS OF DRUG LOADING
2. Electrostatic interaction-The high density of
functional groups like amine or carboxyl on surface of
dendrimer have potential application in enhancing the
solubility of hydrophobic drugs by electrostatic
attractions.
3. Covalent conjugation:The presence of large functional
groups on the surface of dendrimers make them
suitable for covalent conjugation of numerous drugs
with relevant functional groups.
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26. MECHANISM OF DRUG DELIVERY
THROUGH DENDRIMERS
1) In-vivo degradation of drug dendrimer
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27. MECHANISM OF DRUG DELIVERY
THROUGH DENDRIMERS
2) Drug release due to change in physical environment.
Due to change in temperature
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28. MECHANISM OF DRUG DELIVERY
THROUGH DENDRIMERS
Due to change in
pH
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29. APPLICATIONS OF DENDRIMERS
1. Blood substitution: The stearic bulk surrounding a
hememimetic centre significantly slows degradation
compared to free heme.
2. Sensors: Cadmium-sulfide/polypropylenimine
tetrahexacontamine dendrimer composites to detect
fluorescence signal quenching.
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30. APPLICATIONS OF DENDRIMERS
3. Solubility enhancers:
Dendrimers have hydrophobic
core and hydrophilic outer
surface. This enhances
solubility of poorly soluble
drugs by forming cascade and
nonskid-chain like synthesis of
covalent, non covalent
complexes with drug molecules.
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31. APPLICATIONS OF DENDRIMERS
4.Gene transfection: Dendrimers are non-viral gene
transfer agents, enhancing transfection by
endocytosis.
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32. APPLICATIONS OF DENDRIMERS
5. Dendrimers as nanoparticles: Poly(amidoamine)
dendrimers have tertiary amine group at the
branching point. Metal ions are introduced into
aqueous solution of dendrimer and metal ions form
complex with lone pair of electrons present at the
tertiary amines. The ions are then reduced to
zerovalent state to form nanoparticles that is
encapsulated within the dendrimer.
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33. APPLICATIONS OF DENDRIMERS
6. Dendrimers as nano-drugs:
 Polylysine dendrimers with sulfonated naphthyl group
are antiviral.
 PPI dendrimers with tertiary alkyl ammonium groups
attached to the surface are antibacterial
 Chitosan- Dendrimers hybrids have been used as
antibacterial agents.
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34. APPLICATIONS OF DENDRIMERS
7. Dendrimer hydrogel for ocular drug delivery:
 Cross linked networks in dendrimers increase in
volume in aqueous solution.
 Adding PEG groups to dendrimers extends their
application to cartilage tissue production and for
sealing ophthalmic injuries.
 Drug attached to the dendrimers efficiently deliver the
drug to the eyes.
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35. APPLICATIONS OF DENDRIMERS
8. Dendrimers in pulmonary drug delivery:
 Dendrimers have been used for pulmonary delivery of
Enoxaparin.
 G2 and G3 positively charged PAMAM dendrimers
increased bioavailability of drug.
 Positively charged dendrimer forms complex with
enoxaparin.
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36. APPLICATIONS OF DENDRIMERS
9. Dendrimers in transdermal drug delivery:
 Dendrimers improve solubility and plasma circulation
via transdermal formulation.
 PAMAM dendrimers complex with NSAID’S improve
drug permeation through the skin as penetration
enhancers.
 PAMAM-Indomethacin complex as model drug was
reported to be effective.
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37. APPLICATIONS OF DENDRIMERS
10. Dendrimers for targeted drug delivery:
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Active and passive targeting of cancer cells

38. APPLICATIONS OF DENDRIMERS
11. Dendrimers mimicking in angiogenesis:
 Angiogenesis is an important process for tumor growth
initiated by angiogenic factors.
 These factors bind to receptors on endothelial cells
with dependence on heparin.
 Endostatin binds to heparin and prevents
angiogenesis.
 Dendrimers which mimic structure of endostatin
exhibit antiangiogenic activity.
 Eg: TX-1943 AND TX-1944
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39. APPLICATIONS OF DENDRIMERS
12. Dendrimers as carriers or scaffolds for diagnosis
and therapy:
 Medium size dendrimers(5nm) are used for MRI
contrast agents.
 The highly branched dendrimers are used for tissue
engineering applications, cross linking agents,
modulators of surface charge and surface chemistry
and in scaffolds that mimic natural extracellular
matrices.
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40. APPLICATIONS OF DENDRIMERS
Dendrimers in boron neutron capture therapy:
 The cancer patient is injected with boron attach to
dendrimer.
 It migrates to cancerous cells.
 Then irradiate with neutral beam of low energy
neutrons.
 This generates alpha particles which destroy tumour
cells.
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41. APPLICATIONS OF DENDRIMERS
Dendrimers in vaccine development:
 Dendrimers are used as carriers for small antigens,
making it possible to prepare multimeric antigenic
conjugates.
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42. CASE STUDY
 PEGylated nanoparticles accumulate in the tumor tissues
due to the EPR effect. On the surface of a variety of cancer
cells, folate receptors are over expressed. Folate-modified
dendrimers target these cells via ligand receptor
recognition. Folic acid targeted dendrimers which are
covalently conjugated with methotrexate specifically kill
receptor-expressing cells after the intracellular delivery of
the drug through receptor-mediated endocyctosis. In a
study, reseachers synthesized an ethylenediamine core
PAMAM dendrimer of generation 3 which was covalently
attached to folic acid, fluorescein, and methotrexate. This
complex provided targeting, imaging and intracellular drug
delivery capabilities with 100-fold decreased cytotoxicity
over free methotrexate.
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43. CASE STUDY
 In a study, the pH-activated dendrimer was demonstrated
to be a successful drug delivery vehicle system, whereas the
photochemical internalization (PCI) was invented for site-
specific delivery of membrane impermeable
macromolecules from endocytic vesicles into the cytosol.
In this study, doxorubicin (DOX) was conjugated to
polyamidoamine (PAMAM) dendrimers via pH-sensitive
linkers and was combined with different PCI strategies to
evaluate the cytotoxic effects. The results showed that both
PCI strategies significantly improved the cytotoxicity of
free DOX on Cancer cells at higher concentrations. The
'light after' PCI treatment was efficient in releasing DOX
from the PAMAM-hyd-DOX conjugates, resulted in more
nuclear accumulation of DOX and more cell death
through. The results provide invaluable information in the
future design of drug-polymer complexes for multi-
modality cancer treatments.
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44. MARKETED PRODUCTS AVAILABLE
 Several dendrimer based products have been approved by the
FDA. For example, Stratus® CS Acute Care TM(Dade Behring)
was launched for cardiac diagnostic testing ,
 SuperFect TM(Qiagen) is a famous gene transfection agent
applicable to a broad range of cell lines. In addition
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
AstramolTM.
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45. 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.
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46. REFERENCES
 Article on Dendrimers: A tool for drug delivery by Anirudh
Malik, Sudhir Chaudhary, Garima Garg and Avnika Tomar
 Article in Dendrimers as carriers for delivery of
Chemotherapeutic Agents by Scott H. Medina and
Mohamed E. HL- Sayed
 Dendrimers: properties and applications by Barbara
Klajnert and Maria Bryszewska
(http://www.actabp.pl/pdf/1_2001/199.pdf)
 Dendrimers- Nanomaterials
(http://www.sigmaaldrich.com/materials-science/material-
science-products.html)
 Dendrimers by Paul holister and im Harper
(http://www.sps.aero/Key_ComSpace_Articles/TSA-
001_Dendrimers_White%20Paper.pdf)
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47. REFERENCES
 Dendrimers Introduction
(www. nano.med.umich.edu/Platforms/Dendrimers-
Introduction.html)
 Dendrimers as nanocarrier for drug delivery-
Sciencedirect.com(www.sciencedirect.com/science/art
icle/pii/S007960013000853)
 PDF on Dendrimers: A tool for drug delivery- Idosi
(www. idosi.org/abr/6(4)12/6.pdf)
 Dendrimers for drug delivery- Journal of Materials
Chemistry (pubs.rsc.org/en/journals/journal/tb)
 PDF on Dendrimers and their applications as Novel
Drug Delivery by S Tripathy
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48. REFERENCES
 Dendrimers- An Overview
(http://www.pharmainfo.net/reviews/dendrimer-
overview)
 Nanoparticles and cancer therapy: A concise overview
with emphasis on dendrimers
 (http://www.ncbi.nlm.nih.gov/pmcPMC2720735//arti
cles/ )
 PDF on Dendrimers: Design, Synthesis and Chemical
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49. THANKYOU!
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