This document provides an overview of dendrimers, which are highly branched, monodisperse polymeric nanoparticles. It discusses the origins and history of dendrimers, methods for synthesizing them including divergent and convergent approaches, their core-shell structure and properties. Applications of dendrimers mentioned include drug delivery, with mechanisms like encapsulation, electrostatic interactions and covalent conjugation. Characterization techniques and examples of dendrimer types like PAMAM are also summarized.

1. DENDRIMER
Presented by:
Chinchole Pravin Sonu
(M.PHARM 2nd
SEM)
DEPARTMENT OF PHARMACEUTICS & QUALITY
ASSURANCE
R. C. Patel Institute of Pharmaceutical
Education and Research, shirpur.
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2. CONTENT
 INTRODUCTION
 NEED OF DENDRIMERS
 METHODS OF SYNTHESIS
 MECHANISMS OF DRUG DELIVERY
 GENERATION
 TYPES OF DENDRIMERS
 PROPERTIES OF DENDRIMERS
 CHARACTERIZATION OF DENDRIMERS
 APPLICATIONS
 REFERENCES 2

3.  The word “dendrimer” originated from two Greek words,
dendron :- meaning tree,
meros:- meaning part or segment.
 Dendrimers are a new class of polymeric materials. They are
highly branched, monodisperse , artificial
macromolecules.
 Dendrimers may be defined as synthetic three-dimensional
hyper branched, globular macromolecule, which is
characterized by its highly branched 3D structure that
provides a high degree of surface functionality.
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4. HISTORY
 In 1978, Vogtle and co-workers was first introduced
chemistry of Dendrimer .
 In 1980, Donald Tomalia and co-workers discovered, these
hyper branched molecules were called dendrimers.
 In 1985, Vogtle synthesized the first family of dendrimers
the first “cascade molecules”.
 At the same time, Newkome’s groupindependently reported
synthesis of similar macromolecules.
 They called them arborols from the Latin word ‘arbor’ also
meaning a tree.
 The term cascade molecule is also used, but ‘dendrimer’ is
the well established one.
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5.  Dendrimers possess three distinguished components,
namely
(i) An initiator core.
(ii) Interior layers:- composed of repeating units, radically
attached to the interior core(generations).
(iii) Exterior layers :- attached to the outermost interior
generations (terminal functionality).
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6. NEED OF DENDRIMERS:-
 Nano-particle drug-delivery systems are most popular one.
 However reticuloendothelial system (RES) uptake, drug
leakage, immunogenicity, haemolytic toxicity,
cytotoxicity, restrict the use of these nanostructures.
 These are overcome by surface engineering the dendrimer
such as Polyester dendrimer, Glyco-dendrimers, PEGylated
dendrimers etc.
 The bioactive agents can be easily encapsulated into the
interior of the dendrimers.
or
 Chemically attached i.e. physically adsorbed on to the
dendrimer surface.
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7. • Traditional method dendrimer synthesis are:
Michael reaction
Williamson ether synthesis.
 Modern techniques are :
solid-phase synthesis,
organosilicon chemistry,
organo-phosphorus chemistry.
MANUFACTURE COUNTRY DENDRIMERS TRADE
MARK
NAME
CORE
MOLECULE
Dendritech TM U.S.A. PAMAM
dendrimers
Starburst
dendrimers
Ethylenediamine
(EDA) core
DSM Netherlands PPI
dendrimers
Astramol
TM
Butylenediamine
(BDA) core
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8. METHODS OF SYNTHESIS:-
1) Divergent method.
2) Convergent method.
3) Hypercores & branched monomers method.
4) Double Exponential And Mixed Growth.
5) Other accelerated growth technique.
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9. Core surface activation Dendrimer
molecule
 Dendrimers starts from the central core and extends toward the surface
i.e. diverging into space.
 Two step process:
 Activation of functional surface groups
 Addition of branching monomers units.
 Divergent approach is successful for the production of large quantities
of dendrimers.
 It causes some difficulties in the purification of the final
product.
1) Divergent method
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10. Surface unit Monomers Core molecule Dendrimer
2) Convergent method
 Dendrimer starting from the end groups and progressing inwards.
When the growing wedges are enough large, attached to a suitable core
to give a complete Dendrimer.
 The convergent methodology also suffers from low yields in the
synthesis of large structures.
Advantages:
1.Relatively easy to purify the desired product.
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11. 3) Hypercores & Branched Monomers Technique
Frechet group continued their efforts on research of
hypercore & branchad monomers.
This method involves the pre assembly of oligomeric species,
which can then be linked together to give dendrimer.
These monomers allow the to design synthetic strategies that
are more convergent in classical synthetic sense of world.
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12. 4) ‘Double Exponential’ And ‘Mixed’ Growth
 Double exponential growth, similar to a rapid growth
technique for linear polymers, involves an AB2 monomer
with orthogonal protecting groups for the A and B
functionalities.
 This approach allows the preparation of monomers for
both convergent and divergent growth from a single
starting material.
 These two products are reacted together to give an
orthogonally protected trimer, which may be used to repeat
the growth process again.
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13. This is two step approach designed by frechet.
 In this approach two different monomers are used so as to
avoid the need of an activation step between growth steps.
 The two monomeric units are AB2 &CD2.where A&D
reacts to form bond under required conditions while B&C
are stable, where B&C reacts to form bond while A&D
remain stable.
 In this technique the hindrance likely to be experienced is
that difficulty of finding a set of reactions,which conform
to above criteria.
5) Other Accelerated Growth Techniques
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14. The first synthesized dendrimer was Polyamidoamines(PAMAMs)
They are also known as starbust dendrimers.
Ammonia is used as the core molecule & In the presence of methanol, it reacts
with methylacrylate and then ethylenediamine is added By repeating .
The Michael addition & amidation reaction step by step, high generation
dendrimers can be obtained .
Due to their multivalent and monodisperse character, dendrimers have wide
interest in the field of chemistry and biology, especially in applications like drug
delivery, gene therapy and chemotherapy.
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15. Mechanisms of Drug Delivery
 Simple encapsulation:-It directly encapsulates guest
molecules into macromolecule interior.
 Electrostatic interaction:-Surface functional groups
enhances solubility of hydrophobic drugs by electrostatic
interaction e.g. Ibuprofen, ketoprofen, indomethacin.
 Covalent conjugation:-The drug is covalently bound to
dendrimers & its cleavage occurs via chemical or
enzymatic cleavage of hydrolytically labile bonds. It allows
tissue targeting & controlled delivery as drug-dendrimer
conjugate diffuse slower than the free.
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16. GENERATION:-
 The number of focal points when going from the core towards the
dendrimer surface is the generation number.
 That is a dendrimer having five focal points when going from the centre
to the periphery is denoted as the 5th generation dendrimer.
 Here, we abbreviate this term to simply a G5-dendrimer, e.g. a 5th
generation polypropylene imine is abbreviated to a “G5-PPI-
dendrimer.”
 Intermediates during the dendrimer synthesis are sometimes denoted
half-generations, a well-known example is the carboxylic acid-
terminated PAMAM dendrimers.
 Diameter of dendrimer with an ethylenediamine core increases from 1.1
to 12.4 nm.
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17. 17
 PAMAM dendrimers of low generation,G0-G3, have ellipsoidal shapes.
 PAMAM dendrimers of high generations,G4-G10, with well defined cavities
have roughly spherical shapes.

18. TYPES OF DENDRIMERS
1) PAMAM Dendrimers
2 ) PAMAMOS Dendrimers
3 ) PPI Dendrimers
4) TECTO Dendrimers
5) MULTILINGUAL Dendrimers
6 ) CHIRAL Dendrimers
7 ) HYBRID Dendrimers linear polymers
8) AMPHIPHILIC Dendrimers
9) MICELLAR Dendrimers
10) MULTIPLE ANTIGEN PEPTIDE Dendrimers
11) FRECHET-TYPE Dendrimers
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19. Properties Of Dendrimers
Sr.
No
Property Dendrimers Linear Polymers
1 Structure Compact, Globular Not compact
2 Synthesis Careful & stepwise
growth
Single step polycondensation
3 Structural control Very high Low
4 Architecture Regular Irregular
5 Shape Spherical Random coil
6 Aqueous
solubility
High Low
7 Nonpolar
solubility
High Low
8 Viscosity Non linear relationship
with molecular weight
Linear relation with molecular
weight
9 Reactivity High Low
10 Compressibility Low High
11 Polydispersity Monodisperse Polydisperse
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20. CHARACTERIZATION OF DENDRIMERS POLYMERS :-
1. Spectroscopy and Spectrometry Methods
2. Scattering Techniques
3. Electrical Techniques
4. Size Exclusion Chromatography
5. Microscopy
6. Physical Properties & Rheology
7. Miscellaneous
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21. A
P
P
L
I
C
A
T
I
O
N
S
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22. REFERENCES
 “Advances in Controlled & Novel Drug Delivery”, 1st
edition 2001,by Jain N.K,CBS Publications, New
Delhi,361-376.
 “Encyclopedia of Pharmaceutical Technology”, vol-18,by
James swarbrick, Marcel dekker inc,55-89.
 “ Journal of Pharmaceutical sciences”, vol-97,No-1.
January 2008,by American Pharmacists Association,123-
143. 22

23.  “Journal of Pharmaceutical sciences”, vol-98,No-1. January
2009,by American Pharmacists Association,1-26.
 http://en.wikipedia.org/wiki/dendrimer.
 http://www.actabp.pl/pdf/1_2001/199-208.pdf.
 http://www.pharmainfo.net/reviews/dendrimer-overview.
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