Dendrimers in biomedical applications--reflections on the field.

Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications

Dendrimers are versatile, derivatisable, well-defined, compartmentalised chemical polymers with sizes and physicochemical properties resembling those of biomolecules e.g. proteins. The present critical review (citing 158 references) briefly describes dendrimer design, nomenclature and divergent/convergent dendrimer synthesis. The characteristic physicochemical features of dendrimers are highlighted, showing the effect of solvent pH and polarity on their spatial structure. The use of dendrimers in biological systems are reviewed, with emphasis on the biocompatibility of dendrimers, such as in vitro and in vivo cytotoxicity, as well as biopermeability, biostability and immunogenicity. The review deals with numerous applications of dendrimers as tools for efficient multivalent presentation of biological ligands in biospecific recognition, inhibition and targeting.
 Dendrimers may be used as drugs for antibacterial and antiviral treatment and have found use as antitumor agents. The review highlights the use of dendrimers as drug or gene delivery devices in e.g. anticancer therapy, and the design of different host–guest binding motifs directed towards medical applications is described.
 Other specific examples are the use of dendrimers as ‘glycocarriers’ for the controlled multimeric presentation of biologically relevant carbohydrate moieties which are useful for targeting modified tissue in malignant diseases for diagnostic and therapeutic purposes. Finally, the use of specific types of dendrimers as scaffolds for presenting vaccine antigens, especially peptides, for use in vaccines is presented.

Dendrimers in drug research

Dendrimers as carriers for delivery of chemotherapeutic agents.

Dendrimers are characterized by a combination of high end-group functionality and a compact, precisely defined molecular structure. These characteristics can be used in biomedical applications, for example, for the amplification or multiplication of effects on a molecular level, or to create extremely high local concentrations of drugs, molecular labels, or probe moieties. A brief summary of the current state of the art in the field is given, and focuses on the application of dendrimers both in diagnostics as well as in therapy. In diagnostics, dendrimers that bear GdIII complexes are used as contrast agents in magnetic resonance imaging. DNA dendrimers have potential for routine use in high-throughput functional genomic analysis, as well as for DNA biosensors. Dendrimers are also being investigated for therapeutics, for example, as carriers for controlled drug delivery, in gene transfection, as well as in boron neutron-capture therapy. Furthermore, the antimicrobial activity of dendrimers has been studied.

Dendritic polymers in biomedical applications: from potential to clinical use in diagnostics and therapy.

The synthesis of water soluble dendrimers, and their application as possible drug delivery systems

A one pot synthetic approach to amino acid based chiral dendrimers was shown to give good yields for dendrimers with peptide linkages. Using this synthetic strategy, modification of the peripheral functionality is possible, as is the substitution of other amino acids to give mixed amino acid based dendrimers. Immobilization of our dendrimers was accomplished using a coupling method involving the carboxy derivatised dendrimers with an aminopropyl
 modified silica. The use of 2-ethoxy-1-ethoxy-1,2-dihydroquinoline in a one pot protocol gave enhanced reaction conditions from which silicas bearing very high levels of dendrimer were obtained. Solid state NMR analysis substantiated that the dendrimers were bound to the silica and that they appeared to be structurally intact. These
 immobilised chiral dendrimers constitute a new class of chiral stationary phases for use in HPLC.

The synthesis of immobilised chiral dendrimers

The synthesis of two water soluble dendrimers is described. The formation of water soluble inclusion complexes with a variety of small, hydrophobic guest molecules is also described. Moreover, when these guest molecules are drug moieties, then the resulting drug/dendrimer complexes can be considered ideal candidates for use as novel drug delivery systems.

The Synthesis of Water Soluble Dendrimers and Their Application as Possible Drug Delivery Systems.

The reversed phase chromatographic properties of the [G1]-L-glutamic and ethyl ester-AC-silica (1), [G2]-L-glutamic acid ethyl ester-AC-silica (2) and the [G1]-L-glutamic acidt-butyl ester-AC-silica (3) dendrimer stationary phases were evaluated Initial studies involved the comparison between these phases with a classic reversed phase (ie ODS1) by the separation of a standard reversed phase test mixture composed of dimethylphthalate, nitrobenzene, anisole, diphenylamine and fluorene Separations were achieved with comparable performance to those obtained with the conventional reversed phase (ODS1) However, it was apparent that the chromatographic selectivity exhibited by the dendrimer stationary phases was different from that of the ODS1 phase On a per mole basis, the dendrimers exhibited similar (and sometimes greater) affinity for these analytes compared with the ODS1 ligand Subsequent chromatographic experiments were conducted upon the dendrimer chiral stationary phases using chiral analytes under reversed phase and normal phase conditions Chiral resolution was not observed

Martin J. Hardy

Papers

The synthesis of water soluble dendrimers, and their application as possible drug delivery systems

The synthesis of immobilised chiral dendrimers

The Synthesis of Water Soluble Dendrimers and Their Application as Possible Drug Delivery Systems.

Evaluation of Novel Dendrimer Chiral Stationary Phases Using HPLC

Dendripore and dendrilock concepts as new controlled delivery strategies