Dendrimers are considered as the Polymers of 21st century, which ease the process of drug discovery, as we know that current drug discovery techniques takes years of time in inventing new drugs, this new Dendrimers technique help drug discovery companies and pharmaceutical industries to speed up their drug discovery process and provide better results

1. DENDRIMERS POLYMER TECHNIQUE
SPEED UP DRUG DISCOVERY PROCESS
Article written and published by www.worldofchemicals.com

2. ABSTRACT
 Dendrimers are novel and exciting class of highly branched three-
dimensional polymer in which growth emanates from a central core
molecule such as ammonia, ethylenediamine, and polydiamine
or benzene tricarboxylic acid chloride. Dendrimers are considered as the
Polymers of 21st century.
 The discovery and creation of new drugs is timely and costly process. It
is estimated that every new drug takes 12 to 15 years to develop, at a
cost of over $800 million. A controlled release system can improve the
effectiveness of drug delivery by sustained release of the compound
over time or by release at a specific target.
 Currently the two common drug delivery systems are liposomes and
polymeric systems. These both have limited applications, as liposome-
based systems have poor stability and difficulty targeting specific tissues
and linear polymers are polydisperse, there by dendrimers came into
focus to solve these difficulties. Current article will give the basic
concepts, advantages, applications of dendrimers and their role in drug
delivery.

3. INTRODUCTION
 Dendrimers are branched, synthetic polymers with layered architectures that
show promise in several biomedical applications. By regulating dendrimer
synthesis, it is possible to precisely manipulate both their molecular weight and
chemical composition, thereby allowing predictable tuning of their
biocompatibility and pharmacokinetics.
 Advances in our understanding of the role of molecular weight and architecture
on the in vivo behavior of dendrimers, together with recent progress in the
design of biodegradable chemistries, has enabled the application of these
branched polymers as anti-viral drugs, tissue repair scaffolds, targeted carriers
of chemotherapeutics and optical oxygen sensors.
 Dendrimers are repetitively branched molecules. The first dendrimers were
made by divergent synthesis approaches by Fritz Vogtle in 1978, R.G.
Denksewalter at Allied Corporation in 1981, Donald Tomalia at Dow Chemical in
1983, and in 1985, and by George Newkome in 1985. In 1990 a convergent
synthetic approach was introduced by Jean Frechet.
 Dendrimers are large and complex molecules with very well-defined chemical
structures. Dendritic molecules are characterized by structural perfection. They
consist of three major architectural components.
 Core
 Branches
 End/Terminal Groups

4. DENDRIMER STRUCTURE

5. DIFFERENT PROCESS METHODS
 Dendritic architecture is one of the most universal topologies. This
topology provides enhancement of particular properties.
Dendrimers are generally prepared using either a divergent
method or a convergent one. There is a fundamental difference
between these two construction concepts.
 Divergent Method
 Divergent method was introduced by Tomali. In the divergent
method, dendrimer grows outwards from a multifunctional core
molecule. The core molecule reacts with monomer molecules
containing one reactive and two dormant groups giving the first
generation dendrimer. Then the new periphery of the molecule is
activated for reactions with more monomers. The process is
repeated for several generations and a dendrimer is built layer
after layer.

6. PREPARATION OF DENDRIMERS THROUGH
DIVERGENT METHOD

7. CONVERGENT METHOD
 The convergent methods were developed as a response to the
weaknesses of the divergent synthesis. The most attractive
feature of the convergent synthesis is that requires a very small
number of transformations per molecule in the coupling step.
 In the convergent approach, the dendrimer is constructed
stepwise, starting from the end groups and progressing inwards.
When the growing wedges are large enough, several are
attached to a suitable core to give a complete dendrimer.
 Convergent growth method has several advantages like relatively
easy to purify the desired product, occurrence of defects in the
final structure is minimised, does not allow the formation of high
generation dendrimer because stearic problems occur in the
reactions of the dendrons and the core molecule.

8. PREPARATION OF DENDRIMERS THROUGH
CONVERGENT METHOD

9. MECHANISMS OF DRUG DELIVERY
 Encapsulation of drugs
 Dendrimer - drug conjugates
 Encapsulation of drugs
 Kono and coworkers used G3 and G4 ethylenediamine based
polyamidoamine (PAMAM) dendrimers with poly (ethyleneglycol)
monomethyl ether (M-PEG) grafts to encapsulate the anticancer
drugs methotrexate (MTX), and doxorubicin (DOX).
 Higher affinity for MTX was reported based on a greater number
of encapsulated molecules by UV spectroscopy and thus
suggested more favorable acid-base interactions between the
drug and the basic, hydrophobic interior of the dendrimer.
 DOX drug will release faster than MTX from the dendrimer when
measured by diffusion through a dialysis bag. To achieve easier
targeted drug delivery sustained release is preferable. Nature of
drug and dendrimer structure will influence the encapsulation of
drugs.

10. MECHANISMS OF DRUG DELIVERY CONT ..
 Dendrimer-Drug Conjugates
 In 2002, Baker and coworkers conjugated both p-nitrobenzoic
acid by either an amide or ester bond, and DOX by an amide
bond to a G5 capped ammonia based PAMAM dendrimer and
tested the cytotoxic response towards human carcinoma cells.
 Conjugate uptake by cells was measured by a fluorescein tag on
the dendrimers. MTX-FA-dendrimer conjugates entered the cells
with similar uptake to folic acid-dendrimer conjugates while the
dendrimer alone showed less than 10% uptake.
 The amide conjugate was less toxic suggesting that the higher
cytotoxicity for the ester conjugate resulted from intracellular drug
delivery and release.

11. ADVANTAGES
 Dendrimers offers various advantages over other polymers:
 (1) Dendrimers have nanoscopic particle size range from 1-100 nm, which
makes them less susceptible for reticulum endothelium uptake.
 (2) They have lower polydispersity index, due to stringent control during
synthesis. As the density of branches increases the outer most branches
arrange themselves surrounding a lower density core in the form of spheres and
outer surface density is more and most of the space remains hollow towards
core. This region can be utilized for drug entrapment.
 (3) Multiple functional groups are present on outer surface of dendrimers, which
can be used to attach vector devices for targeting to particular site in the body.
 (4) Dendrimers can be modified as stimuli responsive to release drug.
 (5) Dendrimers might show an enhanced permeability and retention effect which
allows them to target tumour cells more effectively than small molecules.
 (6) They can be synthesized and designed for specific applications. Due to their
feasible topology, functionality and dimensions, they are ideal drug delivery
systems, and also, their size is very close to various important biological
polymers and assemblies such as DNA and proteins which are physiologically
idea

12. APPLICATIONS
 The properties of dendrimers like unparalled
molecular uniformity, multifunctional surface and
presence of internal cavities makes it suitable
for a variety of high technology uses.
 Pharmaceutical applications
 Therapeutic applications
 Diagnostic applications
 Dendritic Catalysts / Enzymes
 Industrial Processes

13. CURRENT AND POTENTIAL APPLICATIONS OF
DENDRIMERS
 Single dendrimer molecule has hundreds of possible
sites to couple to an active species. This property of
dendrimers makes researchers to attach both
targeting molecules and drug molecules to the same
dendrimer, which could reduce negative side effects
of medications on healthy cells.
 Alert ticket for Anthrax Detection
 Priofect™, Priostar™ and Starburst for targeted
diagnostic, therapeutic delivery for cancer cells
 SuperFect for Gene Transfection
 Vivagel for preventing HIV

14. CONCLUSION
 Diversified applications for dendrimers can be obtained by
controlling the architecture, shape, branching length and
density, and their surface functionality of dendrimer.
 The high density of surface groups allows attachment of
targeting groups as well as groups that modify the
solution performance or toxicity of dendrimers.
 As the research progresses the dendrimer applications
will integrate into the different sectors and it will helpful to
the universal drug delivery mechanisms.
 The area of dendrimers for drug delivery is continuing to
grow with the recent reports of cascade release
dendrimers and additional ways to release drugs.

15. REFERENCE
 1] Barbara Klajnert, and Maria Bryszewska, Dendrimers:
properties and application, Vol. 48 No. 1/2001, 199–208,
Available from - http://www.actabp.pl/pdf/1_2001/199-
208.pdf
 [2] Catherine A. Brummond, APPLICATIONS OF
DENDRIMERS TO DRUG DELIVERY, March 4, 2004;
Available from-
http://chemistry.illinois.edu/research/organic/seminar_extr
acts/2003_2004/Brummond.pdf
 [3] Tarun Garg, Onkar Singh, Saahil Arora, RSR Murthy,
DENDRIMER- A NOVEL SCAFFOLD FOR DRUG
DELIVERY, Volume 7, Issue 2, Article-039; April 2011-
Available from -
http://globalresearchonline.net/journalcontents/volume7is
sue2/Article-039.pdf