Dendritic polyglycerol: a new versatile biocompatible material
Introduction
Highly branched polymers have become an important interdisciplinary field in current polymer science. A main emphasis in this area has been placed on polymers with tree like or ‘cascade type’ branching, with a branch-on-branch topology. Such materials typically exhibit compact, globular structures in combination with an exceptionally high number of functional groups. Particularly perfect dendrimers have gained enormous attention for biomedical applications due to their unique properties that differ significantly from their linear counterparts (Stiriba et al., 2001). Since the conformation of such polymers is restricted by their molecular architecture, in contrast to linear polymer chains, entanglements are negligible.
Currently, there is rapidly growing interest in this type of material for a variety of biological and medical applications in diagnostics and therapy to molecularly amplify or multiply effects or to create extremely high local concentrations of drugs, molecular labels, or probe moieties. These properties are expected to lead to new strategies for ‘molecular medicine’. Diagnostic applications include dendrimers bearing Gd(III) complexes for magnetic resonance imaging (MRI) to visualize internal organs, tissues and blood vessels (Wiener et al., 1994, Wiener et al., 1996, Adam et al., 1994, Robert et al., 1999). DNA-dendrimers have been developed that show promise for routine use in high throughput functional genomic analysis as well as for DNA biosensors (Hudson and Damha, 1993, Nilsen et al., 1997, Gerhart et al., 2000). Dendrimers are also investigated for therapeutics, i.e. as carriers for controlled drug delivery, for gene transfection (Haensler and Szoka, 1993, Tang et al., 1996), as well as in boron neutron capture therapy (BNCT) (Soloway et al., 1998, Hawthorne and Maderna, 1999). Furthermore, antimicrobial activity of cationic dendrimers and silver complexes is studied (Chen et al., 2000). Finally, the use as homogeneous supports for recyclable catalysts as well as for supported organic and biochemical syntheses has been suggested (Haag, 2001).
Commonly, the perfectly branched dendrimers have been discussed in this context (Fischer and Vögtle, 1999, Bosman et al., 1999). For biomedical applications, aliphatic polyether–polyol dendrimers (Jayaraman and Fréchet, 1998, Grayson et al., 1999, Haag et al., 2000b) have been suggested due to their biocompatible properties (Malik et al., 2000). However, dendrimers have to be prepared in tedious multi-step syntheses, which obviously are a limiting factor for most applications.
In contrast to dendrimers, the less structurally perfect, i.e. randomly branched, hyperbranched polymers synthesized via one-step reactions have been considered as a possible alternative, since structural perfection is not a strict prerequisite for most applications (Sunder et al., 2000a).
Until recently, hyperbranched polymers have been regarded as an insufficient alternative for dendrimers, because they commonly possess broad polydispersity (often Mw/Mn>5!). In addition, their randomly branched architecture (Hölter et al., 1997, Hölter and Frey, 1997, Frey and Hölter, 1999) has been thought to be unsuitable for the construction of complex polymer architectures with for instance, core–shell topology or defined cavities that would permit the entrapment and release of guests. Furthermore, due to intramolecular cyclization during the synthesis (Burgath et al., 2000a), hyperbranched polymers prepared by traditional polycondensation possess no defined single focal point, such as dendrimer segments (‘dendrons’) that permit further monofunctionalization or attachment to a core as well as polymer chains (Hecht and Fréchet, 2001). However, as it is summarized next, recent developments in this area leading to controlled syntheses have opened new possibilities.
Section snippets
Synthesis of well-defined hyperbranched polyglycerols
In the early 1990s, a new concept was introduced that is based on the use of latent ABm monomers, wherein B-groups are set free only upon reaction of the A group, permitting control of molecular weights of the respective hyperbranched polymer (Suzuki et al., 1992, Suzuki et al., 1998). As an alternative to the tedious preparation of such peculiar monomers, we recently developed a convenient pathway to well-defined hyperbranched polyglycerol (Sunder et al., 1999a, Sunder et al., 2000c, Sunder et
Modular synthetic scheme for highly branched polyether
The overview shown in Fig. 3 demonstrates the synthetic versatility of glycidol and related epoxide comonomers. The enormous choice of functional initiator molecules represents the first module (I). Besides non-functionalized Bf-type triol or polyol core molecules, such as trimethylolpropane (TMP) or fatty amine glycidol adducts, initiators with a second functionality can be used, thus, creating the possibility to obtain hyperbranched analogs of dendrimer segments (dendrons) (Sunder et al.,
Biodegradable and biocompatible polymers
Well-defined biodegradable or biocompatible star polymers can be prepared, using polyglycerol or propoxylated polyglycerols as multifunctional initiator core to initiate polymerization of other monomers in a core first approach. For instance, polymerization of ε-caprolactone by Sn catalysts using the polyether polyols as initiators, proceeded smoothly, yielding multiarm stars with biodegradable poly(ε-CL) arms (Burgath et al., 2000b). Such materials are promising with respect to slow or
Conclusions
In this review, we have shown that hyperbranched polyglycerol and its derivatives represent a versatile and promising class of materials for future biomedical applications. The ring opening multibranching polymerization of glycidol can conveniently be scaled up and the resulting materials have recently become commercialized. Derivatives of the resulting highly branched polymers exhibit properties, which so far have been believed to be uniquely restricted to the perfectly branched dendrimers
Acknowledgements
The authors thank the Fonds der Chemischen Industrie for financial support. They are indebted to Dr Alexander Sunder and Dipl. Chem. Holger Kautz as well as many other co-workers that are co-authors in the respective original papers for their valuable contributions to this field as well as many helpful discussions. Furthermore, the authors thank Prof. Rolf Mülhaupt and Hyperpolymers GmbH for their support.
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