2. OUTLINE
• INTRODUCTION
• HISTORICAL BACKGROUND
• STRUCTURES AND COMPONENTS OF
DENDRIMERS
• TYPES OF DENDRIMERS
• SYNTHESIS OF DENDRIMERS
• PROPERTIES OF DENDRIMERS
• METHODS FOR CHARACTERIZATION OF
DENDRIMERS
• APPLICATIONS
3. INTRODUCTION
• A suitable drug delivery system would protect the drug
against degradation and ensure that drug reaches proper
permeability properties and further provides a combined
transportation and protection system against the natural
barriers, as done by the dendrimers. Dendrimers are
highly defined nanoparticles:
– Size: 1 -15 nanometers
– Very versatile surface functionalisation
– Synthetic: Practical and cost effective
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4. HISTORICAL BACKGROUND
• Dendrimers are repetitively branched molecules.
• The term “Dendrimer” arise from two Greek
word :
- “Dendron” meaning tree’
-“Meros” meaning part
• The dendrimers are also called as CASCADE
MOLECULES or ARBOROLS.
5. • Goals behind developing the dendrimers:
A) Modify/Improve the pharmacokinetic and
pharmacodynamic properties of a drug so that there is
also an accretion in bioavailability.
B) Achieve the controlled and targeted release of drug
restricted to the area desired.
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7. STRUCTURE AND COMPONENTS
• A DENDRIMER IS CONSISTS OF:
1. A central core unit.
2. Building blocks with superior interior layers
(generation) composed of repitively units,
radically attached to core .
3. Terminal functional group attached to the
outermost series of branches.
10. PAMAM DENDRIMER
• Poly(amido amine)dendrimers (pamam) are synthesized
by divergent method starting from ammonia or
ethylenediamine initiator core reagents .
• Its available usually as methanol solutions.
• Starburst dendrimers is applied as a trademark name for
a sub class of pamam dendrimers based on a tris-
aminoethyleneimine core .
• The name referred to the star like pattern observed when
looking at the structure of high generation dendrimers of
this type in two dimensions .
11. PAMAMOS DENDRIMER
• Radically layered poly(amidoamine-
organosilicon)dendrimer are inverted
unimolecular miscelles that consists of
hydrophilc ,nucleophilic polyamidoamine
interiors and hydrophobc organosilicon
exteriors .
• Useful as a precursors for the preparation of
honeycomb like networks with nanoscopic
PAMAM and OS domains.
12. MULTIPLE ANTIGEN PEPTIDE
DENDRIMERS:
It’s a dendron like molecular constuct based
upon a polylysine skeleton. Lysine with its
alkyl amino side chain serves as a good
monomer for the introduction of numerous of
branching points.eg: vaccines and diagnostic
research
.
13. FRECHET TYPE DENDRIMER:
These dendrimers usually have carboxylic
acid groups as surface groups, serving as a
good anchoring point for further surface
functionalisation, and as polar surface
groups to increase the solubility of this
hydrophobic dendrimer type in polar
solvents or aqueos media
14. POLY PROPYLENE IMINE
(PPI)DENDRIMER
• These are generally poly-alkyl amines having
primary amines as end groups, the dendrimer
consists of numerous of tertiary tris propylene
amines .
• It is available upto g5, and has found widespread
applications in material science as well as biology.
• As an alternative name to ppi, popam is sometimes
used to describe this class of dendrimers . popam
stands for polypropylene amine.
15. MULTILINGUAL DENDRIMERS:
in these dendrimers, the surface contains multiple copies
of a particular functional group.
HYBRID DENDRIMERS (LINEAR):
These are hybrid(block or graft polymers of dendritic
and linear polymers .
16. AMPHIPHILIC DENDRIMERS:
They are built with two segregated sites of chain
end ,one half is electron donating and the other
half is electron withdrawing.
MISCELLAR DENDRIMERS:
These are unimolecular miscelles of water soluble
hyper branched polyphenylenes.
17. TECTO DENDRIMER :
These are composed of a core dendrimer of
several steps (each type design) to perform a
function necessary for a therpeutic
nanodevice.
Different compounds perform varied
functions ranging from diseased cell
recognition diagnosis of disease state drug
delivery.
19. DIVERGENT SYNTHESIS
• The dendrimer is assembled from a
multifunctional core, which is extended outward
by a series of reactions, commonly a Michael
reaction. Each step of the reaction must be
driven to full completion to prevent mistakes in
the dendrimer, which can cause trailing
generations (some branches are shorter than the
others). Such impurities can impact the
functionality and symmetry of the dendrimer,
but are extremely difficult to purify out because
the relative size difference between perfect and
imperfect dendrimers is very small.
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20. CONVERGENT SYNTHESIS
• Dendrimers are built from small molecules that
end up at the surface of the sphere, and
reactions proceed inward building inward and
are eventually attached to a core. This method
makes it much easier to remove impurities and
shorter branches along the way, so that the final
dendrimer is more monodisperse. However
dendrimers made this way are not as large as
those made by divergent methods, because
crowding due to steric effects along the core is
limiting.
21. 21
Figure 1: Divergent synthesis of dendrimer [4]
Figure 2: Convergent synthesis of dendrimer [4]
22. ADVANTAGES
• DIVERGENT
• Achievement of large molecular dendrimers
• Production of large quantities
• CONVERGENT
• Easy to purify desired product
• Occurrence of defect is minimised
• Possible to incorporate subtle enginnering
23. DISADVANTAGES
• DIVERGENT
• Excess of reagents
• Difficulties in purification
• Possible incomplete reaction with terminal
groups
• Incomplete reaction increases exponentially
• CONVERGENT
• Does not allow formation of high generation
dendrimer because stearic factors occurs in the
reaction of dendron and core molecules.
24. DOUBLE EXPONENTIAL AND MIXED METHOD:
This is a mixture of both divergent and convergent method. In this
method a single starting material is taken from which two monomers
are prepared by divergent and convergent method. Then these two
monomers are reacted together to give an orthogonally protected
trimer. This protecter trimer may be use to repeat the growth process
again. [1]
Figure 3: Combined Divergent-Convergent Method [12]
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25. Table 1: Properties of Dendrimer And Linear Polymers
Serial
Number
Property Dendrimers Linear Polymers
1 Structure Compact and Globular Not compact
2 Shape Spherical Random coil
3 Architecture Regular Irregular
4 Synthesis Stepwise growth Single step
polycondensation
5 Crystallanity Non-crystalline and amorphous
Materials Lower glass
temperatures
Semi crystalline/crystalline
Materials -Higher glass
temperatures
6 Aqueous solubility High Low
7 Nonpolar solubility High Low
8 Compressibility Low High
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26. METHODS FOR CHARACTERIZATION OF
DENDRITIC POLYMERS
Following methods can be used for characterization of
dendritic polymers
.
1.Spectroscopy and spectrometry methods like
Nuclear Magnetic Resonance (NMR), Infra-red (IR) and
Raman, Ultra-violet-visible (UV-VIS), Fluorescence,
Chirality, Optical rotation, Circular dichroism (CD), X-
ray diffraction, and Mass spectrometry
2.Scattering techniques like Small angle X-ray
scattering (SAXS), Small angle neutron scattering
(SANS), and Laser light scattering (LLS)
3.Electrical techniques like Electron paramagnetic
resonance (EPR), Electrochemistry, and Electrophoresis
27. 4.Size exclusion chromatography (SEC)
5.Microscopy like Transmission electron microscopy,
Scanning electron microscopy and atomic force
microscopy
6.Rheology, physical properties like intrinsic
viscosity, Differential Scanning Calorimetry (DSC), and
Dielectric spectroscopy (DS)
7.Miscellaneous like X-ray Photoelectron Spectroscopy
(XPS), measurements of dipole moments, titrimetry, etc
28. APPLICATIONS OF DENDRIMERS
1. Therapeutic Application:
-Dendrimer in photodynamic therapy
-Dendrimers for Boron Neutron capture therapy
2. Pharmaceutical Application:
-Dendrimers in pulmonary drug delivery
-Dendrimers in Transdermal drug delivery
-Dendrimers in ocular drug delivery
-Dendrimers in oral drug delivery
-Dendrimers for controlled release drug delivery
-Dendrimers in targeted drug delivery
-Dendrimers in gene delivery
-Dendrimers as solubility enhancer
-Cellular delivery using Dendrimers carrier
-Dendrimers based product in cosmetics
-Dendrimers based commercial products
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29. 3. Diagnostic Application:
-Dendrimers as MRI contrast agent
-Dendrimers as X-Ray contrast agent
-Dendrimer as molecular probe
4. Dendrimers in Gene Delivery
5. Dendrimers as Solubility Enhancer
6. Dendrimers as Cellular Drug Delivery CarrierDendrimers
in Targeted and Controlled Release Drug Delivery
7. Dendrimers in Cosmetics
8. Dendrimers as a light harvesting antennae [1]
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CONT….
30. REFERENCES
1 S.P.VYAS , R.K.KHAR, Targeted & Controlled drug delivery
systems, CBS Publishers Pvt. Ltd. Pg no-25-27
2. I. Mishra et al, “Dendrimer: A novel drug delivery system”, Journal
of Drug Delivery & Therapeutics, 1st publication, 2nd edition, 2011,
page no. 70-74.
3. V. Babu, V. Mallikarjun, S. Nikhat and G. Srikanth, “Dendrimers: A
New Carrier System For Drug Delivery”, International Journal of
Pharmaceutical and Applied Sciences, 1st edition, 2010, page no. 1-
10.
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