NDDS

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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 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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