Hyperbranched scaffold

In the following sections a detailed analysis of the different hyperbranched scaffolds commonly used in gene delivery is described. Several examples are... 

Dendrimers are a class of macromolecules with a precisely controllable branched structure, consisting of three structural units a core, a hyperbranched scaffold and an external surface [16]. Dendrimers have been shown to possess unusual physical and chemical properties that differ significantly from those of linear oligomers and polymers. By using a fluorescent chromophore as the core of a dendrimer, one can apply fluorescence spectroscopy to study stmctural aspects and the conformational mobility of dendrimers in solution [17, 18]. At the same time, the dendritic shell provides a unique nanometer-sized environment for the spatial isolation of the chromophore, making them interesting materials for investigations by SMS. The synthesis of dendrimers with fluorescent chromophores attached to the rim serves as an efficient way to obtain a weU-defined number of chromophores in a confined volume [19-25]. Not only can the number of chromophores be easily controlled. 

Scheme 9. (A) Different dendrimers as macromolecular scaffolds for MRI contrast agents ethylenediamine cored polyamido amine, generation 4 (PAMAM G4), top hyperbranched, ethylenediamine cored polyethylene imine (HB-PEI), bottom left hyperbranched, amino functionalized polyglycerol (HB-PG), bottom right. (B) Different moieties attached to the respective dendrimers via amide or thiourea bonds.

Scheme 1 Sialoside precursors having varied functionalities for direct attachment to hyperbranched or dendritic scaffolds...

POLY(ETHYLENEIMINE) SCAFFOLD TOWARD HYPERBRANCHED SIALOSIDES... 

Scheme 6 Representative examples of hyperbranched base polymers used for sialic acid attachment and subsequent inhibition of flu virus infection. 14 Poly(ethyleneimine) (PEI) backbone 15 comb-branch polymer 16 dendrigraft polymer 17 PAMAM scaffolded on PEI...

Several amine functionalized hyperbranched PGs have been reported as potential gene delivery systems after a proper surface group functionalization. In comparison to other dendritic structures, these scaffolds have the added advantage of being open, flexible, and possessing a polyether backbone which keeps the toxicity profile low. Different systems have been studied by post-modification of the hydroxyl groups... 

The search for an efficient and non-toxic gene transfection vector has led to the design and synthesis of a great variety of macromolecular scaffolds. An extensive analysis of the key features for the efficient and safe delivery of genes in vivo and in vitro has led to the conclusion that hyperbranched polymers are potential candidates for further development. In this chapter we have presented a detailed analysis of the different hyperbranched polymer scaffolds commonly used in gene delivery applications. Several structural modifications toward the development of an optimal gene vector have been analyzed. 

Chapters 2 and 3 have already introduced the reader to the general principles of the architecture, synthesis, and functionalisation of dendritic molecules - including hyperbranched and dendronised (linear) polymers (denpols). This chapter will now consider specific molecular scaffolds and syntheses of important types of dendrimers and their individual properties. More specialised and appli-cations-relevant properties of particular dendrimers are compiled in Chapter 8. 

Dendritic macromolecules exhibit compact globular structures which lead to their low viscosity in the melt or in solution. Furthermore, dendritic macromolecules are characterized by a very large number of available functional groups, which lead to unprecedented freedom for changing/tuning/tailoring the properties of these multivalent scaffolds via complete or partial derivatization with other chemical moieties. All these features have contributed to multidisciplinary applications of these unique macromolecular structures in recent years 6, 7). The development of efficient synthetic routes in recent years has given rise to a virtually unlimited supply of commercially available dendritic polymers, at very affordable price. The transport properties of hyperbranched and dendritic polymers have recently attracted attention as potentially new barrier and membrane materials 8-9). 

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