This document provides an overview of dendrimers. It begins by defining dendrimers as highly branched macromolecules with a three-dimensional structure that provides high surface functionality. The first dendrimers were synthesized in the late 1970s and early 1980s. Dendrimer design considers architecture, synthesis, and properties/applications. Dendrimers have a spherical, tree-like branching structure built around a core. Higher generation dendrimers become densely packed spheres. There are various types of dendrimers synthesized through divergent, convergent, or mixed methods. Dendrimers find applications in pharmaceuticals such as drug delivery and gene therapy due to their high drug loading capacity.
1. Submitted By
SAIKAT GHOSH
UG-IV
Under the Guidance of
Dr. Ketousetuo Kuotsu
Department of Pharmaceutical Technology,
Jadavpur University
2. The word Dendrimer comes from the Greek word ”DENDRON” meaning tree and
“MEROS” meaning part
A dendrimer is generally described as a macromolecule, which is characterized by
its highly branched 3D structure that provides a high degree of surface functionality
and versatility. Dendrimers have often been referred to as the “Polymers of the 21st
century”.
The first dendrimers were synthesised divergently by Vögtle in 1978, by
Denkewalter and coworkers at Allied Corporation as polylysine dendrimers in
1981, by Donald Tomalia at Dow Chemical in 1983 and in 1985, and by Newkome in
1985. In 1990 a convergent synthesis was introduced by Jean FrechetThey called them
arborols fromthe Latin word ‘arbor’ also meaning a tree.
3. Dendrimer Designing should take into consideration:-
(1) Architecturing
(2) Synthesis
(3) Properties & Applications of the dendrimer
4. STRUCTURE OF DENDRIMERS
Dendrimers are built from a starting atom, such as nitrogen, to which carbon
and other elements are added by a repeating series of chemical reactions that
produce a spherical branching structure
STAR BUST EFFECT:Dendrimers of lower generations- asymmetric shape and
possess moreopen structures - higher generationdendrimers-
globularstructure - become denselypacked - When acritical branched state is
reached-cannot further grow due to lack of space-STAR BUST EFFECT
Fig:STRUCTURE
OF DENDRIMER
8. Synthesis of dendrimers
Monomers lead to a Monodisperse polymer, tree-like, or generational
structure.
There are three defined methods of dendrimer synthesis
Divergent synthesis - assemble the molecule from the core, extending
radially to the periphery
Convergent methods-start at the surface and proceed inwards, before
the attachment of pre-synthesised dendrons to the core.
Double exponential and mixed growth
To synthesize dendrimers repeated reaction consisting of many steps is
needed to protect the active site --it is difficult even if both methods are
used--obstacles to the synthesis of large quantities of dendrimers
9. Different growth methods
Divergent growth method
Advantages of convergent system:-
Relatively easy to purify the desired product
occurrence of defects in the final structure is
minimised.
Possible to introduce subtle engineering into the
dendritic structure by precise placement of
functional groups at the periphery of the Mixed growth & double exponential
macromolecules
10. FACTORS AFFECTING DENDRIMERS
Intrinsic viscosity
Solvent
Effect of p H
Effect of salt
Effect of concentration
Biological like cytotoxicity with increase in
the generations of polymer
Correlation between intrinsic
viscosity and Molecular weight
11. APPLICATIONS OF DENDRIMERS
PHARMACEUTICAL APPLICATIONS
Targeted And Controlled Release Drug
Delivery
Delivery of Anticancer Drugs
The encapsulation of anticancer drugs
Dendrimer As Solubility Enhancers methotraxate (left) and 5-fluorouracil (right) into
PEGylated generation 3 and 4 PAMAM dendrimers
Cellular Delivery Using Dendrimer
Carriers
Dendrimers As Nano-Drugs
Dendrimers In Photodynamic Therapy
Cellular delivery system
12. Dendrimers In Gene Transfection
Dendrimers in gene therapy
Cardiac testing
Boron Neutron Capture Therapy
Dendrimers for Drug and Gene Delivery
Drug Delivery
Gene Delivery
Advancement in Gene Therapy
Dendrimers in tissue engineering
Non-Pharmaceutical Application
Diagnostics-MRI
Dendritic Catalysts / Enzymes
Metallodendritic catalysts
Catalysis with phosphine-based dendrimers
Catalysis with (metallo)dendrimers containing chiral ligands
Non-metal containing dendrimers
Industrial Processes
13. Mechanisms of Drug Delivery
Dendrimers are particularly attractive as they offer a high drug-loading capacity. 2 methods of
dendrimer drug delivery are encapsulation of drugs and dendrimer –drug conjugates
Noncovalent Encapsulation of Drugs
Covalent Dendrimer–Drug Conjugates
Fig:-Different types of drug delivery using dendrimer technology
14. RECENT DEVELOPMENTS
In the field of glycodendrimers
In the field of peptide dendrimers
In the field of PAMAM dendrimers
SAFETY
Conclusion
15. References
1. G.R. Newkome, C.N. Moorefield and F. Vogtle Dendrimers and Dendrons:
Concepts, Syntheses, Applications, Wiley-VCH, New York (2001).
2•. G.M. Dykes , Dendrimers: a review of their appeal and applications. J Chem Technol Biotechnol 76
(2001), pp. 903–918 This review provides basic background information for readers who desire an introduction
to dendrimer chemistry. .
3: Stiriba, H. Frey and R. Haag , Dendritic polymers in biomedical applications: from potential to clinical use in
diagnostics and therapy. Angew Chem Int Ed Engl 41 (2002), pp. 1329–1334.
4. W.B. Turnbull and J.F. Stoddart , Design and synthesis of glycodendrimers. Rev Mol Biotechnol 90 (2002), pp.
231–255
5:J.J. Lundquist and E.J. Toone , The cluster glycoside effect. Chem Rev 102 (2002), pp. 555–578 Many systems
that have been reported for the study of glycocluster–, polymer– and glycodendrimer–protein interactions are
compared. The hemagglutination assay, the enzyme-linked lectin assay, isothermal titration microcalorimetry
and surface plasmon resonance are evaluated
6. N. Rockendorf and T.K. Lindhorst , Glycodendrimers. In: Dendrimers IV, Topics in Current Chemistry
217, Springer-Verlag, New York (2001), pp. 201–238
7. M. Mammen, S-K. Choi and G.M. Whitesides , Polyvalent interactions in biological systems: implications for
design and use of multivalent ligands and inhibitors. Angew Chem Int Ed Engl 37 (1998), pp. 2754–2794.
8 E.K. Woller and M.C. Cloninger , The lectin-binding properties of six generations of mannose-functionalized
dendrimers. Org Lett 4 (2002), pp. 7–10 Binding enhancements for mannose-functionalized dendrimers
relative to methyl mannose were consistent with monovalent interaction (generations 1 and 2), glycoside
clustering (generation 3), and multivalent binding generations 4–6). The wide range of activities that were
observed indicates that dendrimer systems can be fine-tuned to obtain any desired level of activity in protein–
carbohydrate interactions.