Dendrimers are nano-sized, radially symmetric molecules with well-defined, homogeneous, and monodisperse structure consisting of tree-like arms or branches. The second group called synthesized macromolecules ‘arborols’ means, in Latin, ‘trees’. Dendrimers might also be called ‘cascade molecules’ Dendrimers are nearly monodisperse macromolecules that contain symmetric branching units built around a small molecule or a linear polymer core ‘Dendrimer’ is only an architectural motif and not a compound. Dendrimers have gained a broad range of applications in supra molecular chemistry, particularly in host-guest reactions and self-assembly processes.

1. PRESENTED BY ABESH DAS
QUALIFICATION : M.PHARM
DESIGNATION : PROFESSOR
Topic
Dendrimers

2. CONTENTS
• Introduction
• Structure and chemistry
• Classification of Dendrimer
• Approaches for dendrimer
• Convergent Method
• Divergent Method
• Application of dendrimer in biomedical field
• Drugs used with PAMAM Dendrimer

3.  Dendrimers are nano-sized, radially symmetric molecules
with well-defined, homogeneous, and monodisperse
structure consisting of tree-like arms or branches.
 The second group called synthesized macromolecules
‘arborols’ means, in Latin, ‘trees’. Dendrimers might also be
called ‘cascade molecules’
 Dendrimers are nearly monodisperse macromolecules
that contain symmetric branching units built around a
small molecule or a linear polymer core
 ‘Dendrimer’ is only an architectural motif and not a
compound. Dendrimers have gained a broad range of
applications in supra molecular chemistry, particularly in
host-guest reactions and self-assembly processes.
Fig 1 : Dendrimer

4.  Dendrimers are highly defined artificial macromolecules, which are characterized
by a combination of a high number of functional groups and a compact molecular
structure. Dendritic macromolecules tend to linearly increase in diameter and
adopt a more globular shape with increasing dendrimer generation.
 Therefore, dendrimers have become an ideal delivery vehicle candidate for explicit
study of the effects of polymer size, charge, and composition on biologically relevant
properties such as lipid bilayer interactions, cytotoxicity, internalization, blood
plasma retention time, biodistribution, and filtration.
Dendrimer
Molecule
Fig 2 : Dendrimer

5. The structure of dendrimer molecules begins with a central atom or group of
atoms labeled as the core. From this central structure, the branches of other
atoms called ‘dendrons’ grow through a variety of chemical reactions. There
continues to be a debate about the exact structure of dendrimers, in
particular whether they are fully extended with maximum density at the
surface or whether the end-groups fold back into a densely packed interior.
Dendrimers can be prepared with a level of control not attainable with most
linear polymers, leading to nearly monodisperse, globular macromolecules
with a large number of peripheral groups
Fig 3 : Dendrimer Architecture

6. CLASSIFICATION OF DENDRIMERS ON THE
BASIS OF STRUCTURE
Simple Dendrimers. These types of dendrimers consist of simple
monomeric units which are based upon symmetrical substitution of
benzene tricarboxylic acid ester. They have 4, 10, 22, and 46 benzene
rings linked symmetrically and molecular diameters of 45Å.
 Crystalline Dendrimers. These types of dendrimers are formed by
mesogenic monomers which are produced by the functionalization of
carbosylane.
Chiral Dendrimers. In these types of dendrimers, the chirality depends
on the building of 4 constitutionally different but chemically similar
branches to a chiral core, for example, chiral dendrimers obtained from
pentaerythritol
Micellar Dendrimers. These types of dendrimers are fully aromatic,
water-soluble hyperbranched polypropylene dendrimers generating a
cluster of aromatic polymeric chain that is capable to create a milieu that
resembles some micellar structures which results in complex with small
organic molecules in water

7.  Hybrid Dendrimers. These dendrimers are formed by the changes in the
functionalization of peripheral amines of zero generation polyethyleneimine which
results in the formation of structural diverse columnar and cubic-like organized
structures which were significantly transformed to produce dendritic structures, for
example, hybrid dendritic linearpolymers
 Amphiphilic Dendrimers. Amphiphilic dendrimers aremainly prepared by the
segregation of the two sides of the chain with one having electron-withdrawing and the
other part electron-donating, for example, superfect, hydraamphiphiles,and
bolaamphiphiles
 Metallo dendrimers. Metallo dendrimers are formed by acomplex formation method
which takes place either at the peripheral surface or in the interior of the molecule. The
dendrimers formed by this method were found to possess both electrochemical and
luminescence properties, for example,ruthenium bipyridine
 Multilingual Dendrimers. VivaGel is a commercially available multilingual dendrimer.
This contains multiplecopies of a specific group of functions on the surface
 Multiple Antigen Peptide Dendrimers. Multiple antigenpeptide (MAP) dendrimers have
a dendron-like structure formed using the poylysine skelton. Lysine helps in the
conjugationof the alkyloamine side chain which is a monomer for the various branching
units. These types of dendrimers were formed and found to have numerous biological
applications such as in vaccine formation and for diagnostipurposes

9. Fig 4: Convergent Method

10. Fig 5 : Divergent Method

11. APPLICATION OF DENDRIMERS IN
BIOMEDICAL FIELD
• Perhaps to improve pharmacokinetic properties of drugs for cancer the most
promising potential of dendrimers is in their possibility to perform controlled and
specified drug delivery, which regards the topic of nanomedicine.
• Drugs conjugated with polymers are characterized by lengthened half-life and
antigenicity. Unique pathophysiological traits of tumors such as extensive
angiogenesis resulting in hypervascularization, the increased permeability of
tumor vasculature, and limited lymphatic drainage enable passive targeting, and
as a result, selective accumulation of macromolecules in tumor tissue.
• This phenomenon is known as ‘enhanced permeation and retention
 Anticancer Drugs
Fig 6: Dendrimers as drug delivery agents for the treatment of cancer

12.  Transdermal Drug Delivery : Clinical use of NSAIDs is limited due to adverse
reactions such as GI side effects and renal side effects when given orally.
 Transdermal delivery suffers poor rates of transcutaneous delivery due to
barrier
function of the skin.
 Dendrimers have found applications in transdermal drug delivery systems.
Generally, in bioactive drugs having hydrophobic moieties in their structure
and low water solubility, dendrimers are a good choice in the field of efficient
delivery system
 Dendritic sensors : Dendrimers, although are single molecules, can contain
high numbers of functional groups on their surfaces. This makes them
striking for applications where the covalent connection or close proximity of a
high number of species is important.
 Dendrimers as magnetic resonance : imaging contrast agents Dendrimer-
based metal chelates act as magnetic resonance imaging contrast agents.
Dendrimers are extremely appropriate and used as image contrast media
because of their properties

13.  Gene Delivery
• The ability to deliver pieces of DNA to the
required parts of a cell includes many
challenges. Current research is being
performed to find ways to use dendrimers
to traffic genes into cells without damaging
or deactivating the DNA.
• To maintain the activity of DNA during
dehydration, the dendrimer/ DNA
complexes were encapsulated in a water
soluble polymer and then deposited on or
sandwiched in functional polymer films
with a fast degradation rate to mediate
gene transfection.
• Based on this method, PAMAM
dendrimer/DNA complexes were used to
encapsulate functional biodegradable
polymer films for substrate-mediated gene
delivery. Research has shown that the fast-
degrading functional polymer has great
potential for localized transfection
Fig 7: Gene Delivery

14.  Dendrimers used for enhancing
solubility
 PAMAM dendrimers are expected to
have potential applications in
enhancing solubility for drug delivery
systems.
 Dendrimers have hydrophilic exteriors
and interiors, which are responsible for
its unimolecular micelle nature.
 Dendrimer-based carriers offer the
opportunity to enhance the oral
bioavailability of problematic drugs.
 Thus, dendrimer nano carriers offer
the potential to enhance the
bioavailability of drugs that are poorly
soluble and/or substrates for efflux
transporters
Figure 8: Poly (propylene amine)
dendrimer, containing 32 dansyl
units at its periphery

15. DENDRIMERS IN ANTINEOPLASTIC
THERAPY
An increasingly addressed strategy is the use of active molecule carriers,
belonging to nanomaterial technology,
 which aims to improve the target selectivity of drugs in neoplastic cells. Due
to their physicochemical properties, nanoparticles pass biobarriers more
easily.
 The carrier capacity of dendrimers offers an advantage and constitutes an
important strategy in cancer therapy, dendrimers having the role of useful
ligands in transporting the drug molecule to tumor tissue through various
biological compartments, while maximizing the pharmacodynamic activity to
the targeted site.
 Drug release from the dendrimer complex is controlled by different
mechanisms: degradable spacers at specific sites, and the numeric variation
of terminal groups.
 The structure and specific functionality of dendrimer surfaces, correlated with
special properties of these materials, such as high hydrosolubility, allows the
encapsulation/conjugation of several entities, either in the central structure
or on the surface, which makes dendrimers ideal carriers for various

16. Doxorubicin (DOX)—used in lung cancer and brain tumors, and has
been conjugated to PAMAM dendrimers of the fifth generation (G4).
The conjugation was performed via acylhydrazone bonds on the
dendrimer surface, with the advantage of increasing the therapeutic
efficiency and specificity of action in the lung neoplasm, by directing
the pH-controlled DOX-PEG-PAMAM dendrimer
Paclitaxel (PTX)—this was conjugated with a PAMAM G4 dendrimer
through a glycine–phenylalanine–leucine–glycine peptide linker for
the indication of breast cancer. The dendrimeric conjugate increases
specificity and cytotoxicity compared to the PTX molecule alone
Docetaxel (DTX)—the surface modification of PAMAM dendrimers is
a strategy employed to lower systemic toxicity and to increase tumor
targeting . An example of this improvement in efficacy is the case of
DTX, indicated in breast cancer:

17.  Imatinib (IMT)—the PAMAM dendrimer complex of IMT is formed via
electrostatic interactions, as in the case of other hydrophobic acid
molecules, while also non-polar groups of dendrimer ramifications can
act as micelles, increasing solubility.Thus, a PEGylated PAMAM G5
dendrimer conjugate of IMT, a drug used in lung cancer, showed
increased water solubility, and improved targeting and release in
neoplastic cells
 5-fluorouracil (5-FU)—used in gastric neoplasm as an aptamer conjugate
with PAMAM-PEG, it is specifically targeted to MKN45-type neoplastic
cells, with increased uptake by neoplastic cells.
 Sunitinib—used in renal neoplasm, is conjugated with an NH2-PAMAM-
G3 dendrimer through the platinum (II)-based binding system, obtaining
the targeting of the active molecule at the neoplastic renal tissue

18.  The combination of high surface area and
high solubility makes dendrimers useful
as nanoscale catalysts.
 Dendrimers have a multifunctional
surface and all catalytic sites are always
exposed towards the reaction mixture.
They can be recovered from the reaction
mixture by easy ultra filtration methods.
Fig 9: Dendrimer as catalyst
 Dendritic shells can be used to create a microenvironment favorable for
catalysis or provide shielding for functional groups at the dendritic core.
the metal sites in these polymeric catalysts should be easily accessible for
substrate molecules and reagents, and therefore exhibit characteristics-
fast kinetics and solubility

19.  Dendritic shells can be used to create
a microenvironment favorable for
catalysis or provide shielding for
functional groups at the dendritic
core. the metal sites in these well-
deûned polymeric catalysts should be
easily accessible for substrate
molecules and reagents, and therefore
exhibit characteristics- fast kinetics
and solubility
1. Metallodendritic catalysts
2. Catalysis with phosphine-based
dendrimers
3. Catalysis with (metallo)dendrimers
containing chiral ligands
4. Non-metal containing dendrimers
Fig 10 : Internal Structure of
Dendritic shell

20. 1. Dendrimers: Synthetic Strategies, Properties and Applications
urvashi singh, mohammad maqbool dar and athar adil
hashmi*; doi.org/10.13005/ojc/300301
2. Review Article Dendrimers: A New Race of Pharmaceutical
Nanocarriers Pooja Mittal; doi.org/10.1155/2021/8844030
3. Applications and Limitations of Dendrimers in Biomedicine;
Adriana Aurelia Chis, Carmen Dobrea *, Claudiu Morgovan *;
DOI: 10.3390/molecules25173982
4. www.ncbi.nlm.nih.gov/pmc/articles/PMC4074873/