Dendrimers

D E N D I M E R S A NOVEL DRUG DELIVERY SYSTEM

Submitted BySAIKAT GHOSH

UG-IV

Under the Guidance ofDr. Ketousetuo Kuotsu

Department of Pharmaceutical Technology,Jadavpur University

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.

Dendrimer Designing should take into consideration:-(1)Architecturing(2)Synthesis(3) Properties & Applications of the dendrimer

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

COMPONENTS:-(1) Generation (2) Shell(3) Pincer(4) End Group

TYPES OF DENDRIMERS

Pamam Dendrimer

Pamamos Dendrimer

PPI Dendrimer

Tecto Dendrimer

Multilingual Dendrimers

Chiral DendrimersHybrid Dendrimer Linear PolymersAmphiphilic Dendrimers Micellar Dendrimers

Multiple Antigen Peptide Dendrimers Fréchet-Type DendrimersGlycodendrimerPeptide dendrimerFerrocene dendrimerDenderonised polymers

Fig;GLYCODENDRIMER

FIG:PAMAM DENDRIMER

FIG: FERROCENE DENDRIMER

Synthesis of dendrimersMonomers 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

Mixed growth & double exponential

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 macromolecules

FACTORS AFFECTING DENDRIMERS

Correlation between intrinsic viscosity and Molecular weight

Intrinsic viscositySolventEffect of p HEffect of saltEffect of concentrationBiological like cytotoxicity with increase in the generations of polymer

APPLICATIONS OF DENDRIMERS

PHARMACEUTICAL APPLICATIONS

Targeted And Controlled Release Drug Delivery Delivery of Anticancer DrugsDendrimer As Solubility Enhancers

Cellular Delivery Using Dendrimer Carriers

Dendrimers As Nano-Drugs

Dendrimers In Photodynamic Therapy

The encapsulation of anticancer drugs methotraxate (left) and 5-fluorouracil (right) into PEGylated generation 3 and 4 PAMAM dendrimers

Cellular delivery system

Dendrimers In Gene Transfection Dendrimers in gene therapyCardiac testingBoron Neutron Capture TherapyDendrimers for Drug and Gene DeliveryDrug DeliveryGene DeliveryAdvancement in Gene TherapyDendrimers in tissue engineering

Non-Pharmaceutical Application

Diagnostics-MRIDendritic Catalysts / Enzymes Metallodendritic catalysts Catalysis with phosphine-based dendrimers Catalysis with (metallo)dendrimers containing chiral ligandsNon-metal containing dendrimersIndustrial Processes

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

RECENT DEVELOPMENTSIn the field of glycodendrimersIn the field of peptide dendrimersIn the field of PAMAM dendrimers

SAFETY

Conclusion

References1. 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. 231–2555: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 evaluated6. N. Rockendorf and T.K. Lindhorst , Glycodendrimers. In: Dendrimers IV, Topics in Current Chemistry 217, Springer-Verlag, New York (2001), pp. 201–2387. 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.

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