Submitted By SAIKAT GHOSH UG-IV Under the Guidance of Dr. Ketousetuo KuotsuDepartment of Pharmaceutical Technology, Jadavpur University
The word Dendrimer comes from the Greek word ”DENDRON” meaning tree and“MEROS” meaning partA dendrimer is generally described as a macromolecule, which is characterized byits highly branched 3D structure that provides a high degree of surface functionalityand versatility. Dendrimers have often been referred to as the “Polymers of the 21stcentury”.The first dendrimers were synthesised divergently by Vögtle in 1978, byDenkewalter and coworkers at Allied Corporation as polylysine dendrimers in1981, by Donald Tomalia at Dow Chemical in 1983 and in 1985, and by Newkome in1985. In 1990 a convergent synthesis was introduced by Jean FrechetThey called themarborols 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 DENDRIMERSDendrimers are built from a starting atom, such as nitrogen, to which carbonand other elements are added by a repeating series of chemical reactions thatproduce a spherical branching structureSTAR BUST EFFECT:Dendrimers of lower generations- asymmetric shape andpossess moreopen structures - higher generationdendrimers-globularstructure - become denselypacked - When acritical branched state isreached-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
Synthesis of dendrimersMonomers lead to a Monodisperse polymer, tree-like, or generationalstructure.There are three defined methods of dendrimer synthesisDivergent synthesis - assemble the molecule from the core, extendingradially to the peripheryConvergent methods-start at the surface and proceed inwards, beforethe attachment of pre-synthesised dendrons to the core.Double exponential and mixed growthTo synthesize dendrimers repeated reaction consisting of many steps isneeded to protect the active site --it is difficult even if both methods areused--obstacles to the synthesis of large quantities of dendrimers
Different growth methods Divergent growth methodAdvantages of convergent system:-Relatively easy to purify the desired productoccurrence of defects in the final structure isminimised.Possible to introduce subtle engineering into thedendritic structure by precise placement offunctional groups at the periphery of the Mixed growth & double exponentialmacromolecules
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
APPLICATIONS OF DENDRIMERSPHARMACEUTICAL APPLICATIONSTargeted And Controlled Release Drug DeliveryDelivery of Anticancer Drugs The encapsulation of anticancer drugsDendrimer As Solubility Enhancers methotraxate (left) and 5-fluorouracil (right) into PEGylated generation 3 and 4 PAMAM dendrimersCellular Delivery Using Dendrimer CarriersDendrimers As Nano-DrugsDendrimers In Photodynamic Therapy Cellular delivery system
Dendrimers In Gene TransfectionDendrimers in gene therapyCardiac testingBoron Neutron Capture TherapyDendrimers for Drug and Gene DeliveryDrug DeliveryGene DeliveryAdvancement in Gene TherapyDendrimers in tissue engineeringNon-Pharmaceutical ApplicationDiagnostics-MRIDendritic Catalysts / EnzymesMetallodendritic catalysts Catalysis with phosphine-based dendrimersCatalysis with (metallo)dendrimers containing chiral ligandsNon-metal containing dendrimersIndustrial Processes
Mechanisms of Drug DeliveryDendrimers are particularly attractive as they offer a high drug-loading capacity. 2 methods ofdendrimer drug delivery are encapsulation of drugs and dendrimer –drug conjugatesNoncovalent Encapsulation of DrugsCovalent 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 dendrimersSAFETYConclusion
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 introductionto dendrimer chemistry. .3: Stiriba, H. Frey and R. Haag , Dendritic polymers in biomedical applications: from potential to clinical use indiagnostics 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 systemsthat have been reported for the study of glycocluster–, polymer– and glycodendrimer–protein interactions arecompared. The hemagglutination assay, the enzyme-linked lectin assay, isothermal titration microcalorimetryand surface plasmon resonance are evaluated6. N. Rockendorf and T.K. Lindhorst , Glycodendrimers. In: Dendrimers IV, Topics in Current Chemistry217, Springer-Verlag, New York (2001), pp. 201–2387. M. Mammen, S-K. Choi and G.M. Whitesides , Polyvalent interactions in biological systems: implications fordesign 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-functionalizeddendrimers. Org Lett 4 (2002), pp. 7–10 Binding enhancements for mannose-functionalized dendrimersrelative to methyl mannose were consistent with monovalent interaction (generations 1 and 2), glycosideclustering (generation 3), and multivalent binding generations 4–6). The wide range of activities that wereobserved indicates that dendrimer systems can be fine-tuned to obtain any desired level of activity in protein–carbohydrate interactions.