Introduction Types Composition Mechanism of Action Advantages & Disadvantages Characterization Methods of Preparation Application

1. 1
DENDRIMERS
Dr. Anil Pethe
Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management,
SVKM’S NMIMS, Mumbai

2. Introduction
Types
Composition
Mechanism of Action
Advantages & Disadvantages
Characterization
Methods of Preparation
Application
Contents

3. • 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.
What are Dendrimers

4. • In 2008 there were over 10 000 scientific reports and 1000 patents dealing with
dendritic structures.
• Tree-like polymers, branching out from a central core and subdividing into
hierarchical branching units
 Not more that 15 nm in size, Mol. Wt very high
 Very dense surface surrounding a relatively hollow core (vs. the linear
structure in traditional polymers)
What are Dendrimers

5. 1) An interior core
2) Interior layers composed of repeating units radically attached to cores.
3) Exterior layer (terminal functionality) attached to interior generations.
Structure of Dendrimers

6. 3-D Structure of Dendrimers

7. Dendritic Family

8. Types of Dendrimers
Types of
Dendrimers
PAMAM
Dendrimer
PPI
Dendrimer
Chiral
Dendrimer
Multilingual
Dendrimer
Techto
Dendrimer
Hybrid
Dendrimer
Ampiphilic
Dendrimer
Frechet type
Dendrimer
Peptide
Dendrimer
PAMAMOS
Dendrimer

9. • 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.
• 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 of the high generation dendrimers of this
type in two-dimensions
PAMAM Dendrimer

10. • PAMAMOS Dendrimer – PAMAMOS or Poly
(Amido Amine Organosilicon) are silicon
containing first commercial dendrimers.
• These are inverted unimolecular micelles
that consist of hydrophilic, 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.
PAMAMOS Dendrimer

11. • 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.
• 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.
PPI Dendrimer

12. • 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.
Tecto Dendrimer

13. • Frechet-Type Dendrimers – It is a more recent type of dendrimer
developed by Hawker and Frechet based on polybenzyl ether hyper
branched skeleton.
• These dendrimers usually have carboxylic acid groups as surface
groups, serving as a good anchoring point for further surface
fictionalization, and as polar surface groups to increase the solubility
of this hydrophobic dendrimer type in polar solvents or aqueous
media.
Frechet Type Dendrimer

14. • Amphiphilic Dendrimers – These are composed of two segregated
sites of chain end, one half is electron donating and the other half is
electron withdrawing.
Amphiphilic Dendrimer

15. • Hybrid Dendrimers – These are hybrids (block or graft polymers) of
dendritic and linear polymers having characters of both.
• Hybrid dendrimers are obtained by complete mono functionalization of
the peripheral amines of a "zero generation” polyethyleneimine
dendrimer; provide structurally diverse lamellar, columnar, and cubic self
organized lattices that are less readily available from other modified
dendritic structures.
Hybrid Dendrimer

16. • Chiral Dendrimers – The chirality in
these dendrimers is based upon the
construction of constitutionally
different but chemically similar
branches to the chiral core.
• Their potential use as chiral hosts
for enantiomeric resolutions and as
chiral catalysts for asymmetric
synthesis has been recognized.
Chiral Dendrimer

17. • Peptide Dendrimers – These dendrimers consists of amino acids as
branching or interior unit. It is a dendron like molecular construct based
upon a polylysine skeleton.
• This type of dendrimer was introduced by J. P. Tam in 1988, has
predominantly found its use in biological applications, such as in vaccine
and diagnostic research.
Peptide Dendrimer

18.  Divergent method
 Convergent method
 Double Exponential and Mixed Growth
 Hypercores and Branched Monomers Growth
Synthesis of Dendrimers

20. • Dendrimer grows from core to periphery.
• The core molecule reacts with the monomer molecule having two
dormant and one reactive group.
Divergent method

21. • 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.
• Small molecules come together and reaction proceeds inward.
• Eventually the molecules become attached to the core.
Convergent method

23. • 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.
• Strength of double exponential growth is more subtle than the ability to
build large dendrimers in relatively few steps.
Double Exponential and Mixed Growth

24. • This method involves the pre-assembly of oligomeric species which can be linked
together to give dendrimers in fewer steps or higher yields in a radial, branch-
upon-branch.
• Core is reacted with two or more moles of reagent containing at least two
protecting branching sites, followed by removal of the protecting groups.
• The subsequent liberated reactive sites lead to the first generation Dendrimers.
Hypercores and Branched Monomers Growth

25. • Inert and non-toxic;
• Biodegradable;
• Non-immunogenic;
• Able to cross barriers such as intestine, blood-tissue barriers, cell membranes etc;
• Able to stay in circulation for the time needed to have a clinical effect;
• Able to target to specific structures;
• Compatible with guest molecules;
• Must protect the drug until it reaches to the desired site of action and release the
drug.
Ideal Properties of Dendrimers

26. Drugs
Drug delivery –
 Small molecules
 Proteins
 Tissue targeting
Drug solublization
RNA/DNA delivery
Diagnostics & materials applications
Applications of Dendrimers

27.  Improved efficacy of drugs
 Extension of drug half-life
 Reduced toxicity
 Active or passive targeting
 Product lifecycle management
 Improved solubility of drugs
 Drug “rescue”
Applications in drug delivery

28. • Utilizing a dendrimer construct the aqueous solubility of
the drug Paclitaxel was increased >9,000X.
Paclitaxel aqueous solubility 0.8 mg/mL
Improved Drug Solubility

29. • Dendrimers are particularly attractive as they offer a high
drug-loading capacity.
• Methods of dendrimer drug delivery are
Encapsulation of drugs
Dendrimer –drug conjugates
Mechanism of drug delivery: Dendrimer

30. 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.
Mechanism of drug delivery: Dendrimer
Encapsulation of drugs

31. 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
Mechanism of drug delivery: Dendrimer

32. The drug loading can be tuned by varying the generation number of
the dendrimer
Release of the drug can be controlled by incorporating degradable
linkages between the drug and dendrimer
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
Mechanism of drug delivery: Dendrimer

33. Drugs Delivered Through Dendrimers