dendrimers in detail

1. Presented by – Ms. Sayali P. Nagrale
Subject – Advance pharmacuetics
Class -M.Pharm (sem I)
Department -pharmaceutics
Guided by – Dr. Namita Desai and
Dr. Prachi Mehendale

2. CONTENTS
 INTRODUCTION
 COMPOSITION OF DENDRIMERS
 PROPERTIES OF DENDRIMERS
 TYPES OF DENDRIMERS
 METHOD OF SYNTHESIS
 CHARACTERIZATION OF DENDRIMERS POLYMERS
 APPLICATION
 MECHANISM OF DRUG DELIVERY
 REFRENCE

3.  They are family of nanosized, highly branched three dimensional molecules.
 Dendrimers may be defined as synthetic polymeric , hyper branched globular
macromolecule, which is characterized by its highly branched 3D structure
that provides a high degree of surface functionality.
WHAT ARE DENDRIMERS ?
 The word “Dendrimer” originated from two Greek words,
“dendron” meaning tree,
“meros” meaning part or segment.

4.  A dendrimer have a Tree-like structure , branching out from a central core
and subdividing into hierarchical branching units
 Very dense surface surrounding a relatively hollow core

5.  Size of dendrimer is usually in range from 1nm – 10’s of nm , with high molecular
weight .
 Comparatively , the general size of a dendrimer is larger than a typically closed
fullerene having a diameter of 0.7nm and smaller than a amino microsphere that
is having a diameter between 0.1 -10 µm .
 The size of dendrimer depends upon the number of steps which are used for
them as building as dendrimers are constructed by stepwise connection of several
parts .

6. COMPOSITION OF DENDRIMER

7. COMPOSITION OF DENDRIMER
Dendrimers possess three distinguished components, namely
(i) An initiator core :-structurally a dendrimer begins at a multifunctional
core. Numerous molecules like ammonia, benzene, porphyrine or fullerene
can be used as dendrimer core.
(ii) Interior layers:- composed of repeating units, which are radically attached
to the interior core (generations).
(iii) Exterior layers :- These are attached to the outermost interior generations
(terminal functionality).

8. What is generation number ?
• The number of focal points ( branching point ) when going from the core
towards the dendrimer surface is the generation number.
• That is a dendrimer having four focal points when going from the center to the
periphery is denoted as the 4th generation dendrimer.

9. • 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.

10. PROPERTIES OF DENDRIMER

11. Sr
.No.
PROPERTY DESCRIPTION
1 Monodispersity Dendrimers are constructed with well defined molecular structure.
Verified by HPLC
2 Nanoscale size and shape Dendrimers have nanoscale dimensions due to their well-organized
synthesis strategy and size controllable properties.
3 Polyvalency The outer shell of a dendrimer admits functionalisation fairly easy,
allowing multiple functionalities to be added. Polyvalency is useful as
it provides versatile functionalisation
4 Loading capacity In addition to carrying materials on their surface, the internal cavities
of dendritic structures can be used to carry and/or store a wide range
of metals, organic, or inorganic molecules by encapsulation and
absorption
5 Biocompatibility Dendrimers should be
-non toxic ,non-immunogenic ,biopermeable, retain in circulation for
intended time ,able to target specific structure

12. SYNTHESIS OF DENDRIMERS
Synthesis of
dendrimers
Divergent
method
Convergent
method
Double
exponential and
mixed growth
Hypercore and
branched
technique

13. DIVERGENT METHOD
 Dendrimer grows from core to periphery.
 Two step process
1. activation of functional group
2. addition of branching monomers unit
 divergent approach is successful for the production of large quantities of
dendrimers.

14. CONVERGENT METHOD
 Dendrimer growth starting from end groups and progresses inward.
 When the growing wedges are large enough , attached to suitable core to
give a complete dendrimer
 Advantage :
relatively easy to purify the desired product .

16. DOUBLE EXPONENTIAL AND MIXED GROWTH
 In this approach two products (monomers for both convergent and divergent
growth) are reacted together to give an orthogonally protected trimer, which
may be used to repeat the growth process again
 These allows the preparation of monomers for both convergent and divergent
growth starting material .

17. HYPERCORE AND BRANCHED TECHNIQUE
Core hypercore 4th gen. dendrimer
 This method involves pre-assembly of oligomeric species , which can then
be linked together to give dendrimer.

18. DENDRIMER GROWTH MONITORING
 An inherent challenge that accompanies the synthesis of dendrimers is the risk
of either incomplete substitution during the growth or activation of the
dormant species.
 In both cases, structural defects will be present and separation of the perfect
from less perfect dendrimer is almost impossible . Structural defects can be
circumvented by utilizing organic reactions that are known for their robustness
and high fidelity at macromolecular level as well as the employment of MS
technique that can monitor the progress of the reaction.

19.  A typical monitoring by MALDI-TOF MS of the dendrimer growth can be
visualized, in this case from G3 to G4.
 In the case where the growth is not complete within a realistic time
frame, addition of more monomers, a catalyst and heat may be
necessary to allow the complete growth of the dendrimer.
 In should be noted that dendrimer synthesis via inside-out approach is
the most viable approach as the strategy only requires an excess of
inexpensive monomers and reagents

20. 1. PAMAM Dendrimer
2. PPI Dendrimer
3. Chiral Dendrimer
4. Techto Dendrimer
5. Hybrid Dendrimer
6. Ampiphilic Dendrimer
7. Frechet type Dendrimer
8. Peptide Dendrimer
9. PAMAMOS Dendrimer
10. Micellar dendrimer
Types of
Dendrimers

21. 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.
 PAMAM dendrimers are commercially available, usually as methanol
solutions.

22.  Starburst dendrimers is applied as a trademark name for a sub-class of
PAMAM dendrimers based on a trisaminoethylene-imine core.
 The name refers to the star like pattern observed when looking at the
structure .

23. PAMAMOS DENDRIMER
 PAMAMOS or Poly (Amido Amine Organosilicon) are silicon containing first
commercial dendrimers.
 These are inverted unimolecular
micelles that consist of hydrophilic core ,
nucleophilic polyamidoamine (PAMAM)
interiors and hydrophobic organosilicon
(OS) exteriors.
 These dendrimers are exceptionally useful precursors for the preparation of
honeycomb-like networks with nanoscopic PAMAM and OS domains

24. PPI DENDRIMER
 PPI or Poly (Propylene Imine)/ Poly (Propylene Amine) is one of the
oldest known dendrimer developed initially by Vogtle.
 Its core structure is based on diamino butane with primary amines as
end groups and tertiary propylene amines as interior.
 Thus, these dendrimers are also sometimes referred to as “DAB-
dendrimers” where DAB refers to the core structure, which is usually
based on Diamino butane.

25.  PPI dendrimers are commercially available up to G5, and has found
widespread applications in the field of material science and biology. These
are widely available as Astramol TM.

26. TECTO DENDRIMER
 These are composed of a core dendrimer, surrounded by other
dendrimers, each one of which perform a specific function leading to a
smart therapeutic system which can simultaneously diagnose the
diseased state and deliver API to the recognized diseased cell.
 Different compounds perform varied
functions ranging from diseased cell
recognition, diagnosis of disease state,
drug delivery, reporting outcomes of therapy.

27.  Various characterization techniques such as elemental analysis ,
chromatography (HPLC) , NMR spectroscopy are used . But small amount
of impurities are generally not exposed in higher generation dendrimer
Some other techniques :
1. Scattering Techniques
2. Electrical Techniques
3. Microscopy
4. Electrophoresis
CHARACTERIZATION OF DENDRIMER

28. APPLICATIONS OF DENDRIMERS
 Dendrimers in boron neutron capture therapy
Boron therapy is related with the treatment of cancers that is supported
Boron capture reaction .The applicability of PAMAM dendrimers in investigating
intratumoral delivery of agents for neutron capture therapy is remarkable in
bioscience.
 Dendrimers as imaging agents
Visualizing both tumor vasculature and lymphatic involvement using
Gadolinium (III) (Gd) the paramagnetic contrast agent. Recently PEG conjugated
polyester dendrimer is used . This dendrimer conjugate contrasting agent has
shown to supply enhanced contrast than commercially available product
Magnevist®

29.  Dendrimers in Oral Drug Delivery
It is suitable candidate in oral drug delivery because it loosened the tight
junctions of epithelial layer and thus an improvement within the absorption of
small relative molecular mass drugs is achieved
 Dendrimers in Intravenous Drug Delivery
The intravenous route is the simplest method for delivering a drug into the
circulation. However, poor water solubility of the many drugs, especially anti-
cancer drugs, limits the applying of intravenous administration route in clinical
trials. After using PAMAM dendrimers it was observed that these materials
were cleared rapidly from the blood via the kidney during the primary day post
injection.

30.  Dendrimers in Vaccine Development
With In the field of vaccine design, dendrimers may be used as model
molecules to host immune +-stimulators and/or antigens
 Dendrimers in Cell Repair
For regeneration of porcine tissue, Poly amido amine dendrimer generation
1.0 is used. Another application of dendrimers during this field corresponds to in
vitro bone tissue reconstruction.
 Dendrimers in Site Specific Drug Delivery
The location specific delivery of the drug might be achieved by surface
modification of dendrimers employing various targeting moieties like folic acid
(FA), peptides, monoclonal antibodies and sugar groups

31.  Dendrimers as Anti-cancer Drug Carriers.
The most promising uses of dendrimers are as drug carriers due to their
globular shape and their combined hydrophobic and hydrophilic character.
sr.no. Anti-cancer drug Dendrimer type
1 CDDP( Cisplatin ) PAMAM
PAMAM-COOH
2 MTX(Methotrexate) Polyether-co-polyester PAMAM
Poly Glycerol
3 PTX(Paclitaxel) PAMAM
PPI
4 DOX(Doxorubicin ) PEGylated-PAMAM
Poly ester

32. METHODS OF DENDRIMER DRUG DELIVERY
DENDRIMERS ARE PARTICULARLY ATTRACTIVE AS THEY OFFER A HIGH DRUG-
LOADING CAPACITY.
• METHODS OF DENDRIMER DRUG DELIVERY ARE
1. ENCAPSULATION OF DRUGS
2. DENDRIMER –DRUG CONJUGATES

33. DENDRIMER ENCAPSULATION OF DRUGS
 Interactions between the dendrimer and
drug to trap the drug inside the dendrimer.
Such a system can be used to encapsulate
drugs and provide controlled delivery.
 eg: DNA was complexed with PAMAM
dendrimers for gene delivery applications,
and hydrophobic drugs and dye molecules
were incorporated into various dendrimer
cores.

34. DENDRIMER–DRUG CONJUGATES
 In dendrimer–drug conjugates, the drug is attached through a covalent bond
either directly or via a linker/spacer to the surface groups of a dendrimer.
 Dendrimers have been conjugated to various biologically active molecules
such as drugs, antibodies, sugar moieties and lipids
 Conjugates of PAMAM dendrimers with cisplatin, a potent anticancer drug
with non-specific toxicity and poor water solubility.
 The conjugates show increased solubility, decreased systemic toxicity and
selective accumulation in solid tumors .

35. CONCLUSION
 Dendrimers are an excellent drug delivery system and holds promising
future in various fields like pharmaceutical, therapeutic, and diagnostics
due to their specific characteristics .
 Dendrimers are expected to play a key role in biomedical fields in future
as they provide platforms for drug attachment and have the ability to
encapsulate or bind drugs via several mechanisms.

36. REFERENCES
 Priya.P, Sivabalan ,Mand Jeyapragash.R , “Review Article: DENDRIMER: A NOVEL POLYMER” International
journal of research in pharmacy and chemistry www.ijrpc.com
 Pavankumar balagani, Sindhuri Manubolu , “Dendrimer: a complete drug carrier”
Article · January 2011https://www.researchgate.net/publication/260273242
 Shyma M.S, Sheri P.S “Dendrimers- A Emerging Tool For Drug Delivery” J. Pharm. Sci. & Res. Vol. 12(10),
2020, 1309-1314
 P. Anitha, j. Bhargavi, g. Sravani, b. Aruna, ramkanth s “Review Article :Recent progress of dendrimers in
drug delivery for cancer therapy” Int J App Pharm, Vol 10, Issue 5, 2018.
 Dr. Nama Sreekanth, Brahmaiah Bonthagarala, Prasanna kumar desu “Dendrimer-Emerging Polymers for
Drug Delivery and It's Future Prospects“ Article · January
2019https://www.researchgate.net/publication/330193589